Protein crystallography in vaccine research and development

International Journal of Molecular Sciences

Volumn 16, Issue 6, 2015, Pages 13106-13140

  Malito, Enrico ^a   Carfi, Andrea ^b   Bottomley, Matthew J ^a  

^a NOVARTIS VACCINES AND DIAGNOSTICS   (Italy)

^b GLAXOSMITHKLINE   (United States)

Author keywords

Crystallization; Human immunodeficiency virus (HIV); Meningitis; Paratope; Protein engineering; Respiratory syncytial virus (RSV); Staphylococcus aureus

Indexed keywords

ADHESIN; BACTERIAL ANTIGEN; FACTOR H BINDING PROTEIN; GLYCOPROTEIN GP 120; GLYCOPROTEIN GP 41; HUMAN IMMUNODEFICIENCY VIRUS ANTIGEN; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; MENINGOCOCCUS VACCINE; MOTAVIZUMAB; NADA ANTIGEN; NEISSERIAL HEPARIN BINDING ANTIGEN; PALIVIZUMAB; RESPIRATORY SYNCYTIAL VIRUS VACCINE; STAPHYLOCOCCAL SOLUTE BINDING PROTEIN ANTIGEN; TRANSFERRIN BINDING PROTEIN B; UNCLASSIFIED DRUG; VACCINE; EPITOPE; RECOMBINANT VACCINE; VIRUS ANTIGEN;

ANTIBODY COMBINING SITE; ANTIGEN ANTIBODY COMPLEX; ANTIGEN STRUCTURE; CRYSTAL STRUCTURE; CRYSTALLIZATION; DRUG DESIGN; ELECTRON MICROSCOPY; EPITOPE MAPPING; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; IMMUNOGENICITY; MASS SPECTROMETRY; NEISSERIA MENINGITIDIS; NONHUMAN; PROTEIN ENGINEERING; REVIEW; STRUCTURAL GENOMICS; SYNCHROTRON; X RAY CRYSTALLOGRAPHY; AMINO ACID SEQUENCE; CHEMISTRY; CRYSTALLOGRAPHY; IMMUNOLOGY; MOLECULAR GENETICS;

HUMAN IMMUNODEFICIENCY VIRUS; RESPIRATORY SYNCYTIAL VIRUS; STAPHYLOCOCCUS AUREUS;

AMINO ACID SEQUENCE; ANTIGENS, BACTERIAL; ANTIGENS, VIRAL; BINDING SITES, ANTIBODY; CRYSTALLOGRAPHY; EPITOPES; MOLECULAR SEQUENCE DATA; VACCINES, SYNTHETIC;

EID: 84931292286     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms160613106     Document Type: Review

References (180)

1. Plotkin, S.; History of vaccination. Proc. Natl. Acad. Sci. USA 2014, 111, 12283-12287.
2. Whitney, C.G.; Zhou, F.; Singleton, J.; Schuchat, A. Benefits from immunization during the vaccines for children program era—United States, 1994-2013. Morb. Mortal. Wkly. Rep. 2014, 63, 352-355.
3. Delany, I.; Rappuoli, R.; de Gregorio, E. Vaccines for the 21st century. EMBO Mol. Med. 2014, 6, 708-720.
4. Rappuoli, R. Reverse vaccinology, a genome-based approach to vaccine development. Vaccine 2001, 19, 2688-2691.
5. Pizza, M.; Scarlato, V.; Masignani, V.; Giuliani, M.M.; Arico, B.; Comanducci, M.; Jennings, G.T.; Baldi, L.; Bartolini, E.; Capecchi, B., et al. Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science 2000, 287, 1816-1820.
6. Giuliani, M.M.; Adu-Bobie, J.; Comanducci, M.; Arico, B.; Savino, S.; Santini, L.; Brunelli, B.; Bambini, S.; Biolchi, A.; Capecchi, B., et al. A universal vaccine for serogroup B meningococcus. Proc. Natl. Acad. Sci. USA 2006, 103, 10834-10839.
7. Pace, D.; Pollard, A.J. Meningococcal disease: Clinical presentation and sequelae. Vaccine 2012, 30 (Suppl. 2), B3-B9.
8. Pace, D. Quadrivalent meningococcal ACYW-135 glycoconjugate vaccine for broader protection from infancy. Expert Rev. Vaccines 2009, 8, 529-542.
9. Finne, J.; Bitter-Suermann, D.; Goridis, C.; Finne, U.; An IgG monoclonal antibody to group B meningococci cross-reacts with developmentally regulated polysialic acid units of glycoproteins in neural and extraneural tissues. J. Immunol. 1987, 138, 4402-4407.
10. O’Ryan, M.; Stoddard, J.; Toneatto, D.; Wassil, J.; Dull, P.M.; A multi-component meningococcal serogroup B vaccine (4CMenB): The clinical development program. Drugs 2014, 74, 15-30.
11. Zlotnick, G.W.; Jones, T.R.; Liberator, P.; Hao, L.; Harris, S.; McNeil, L.K.; Zhu, D.; Perez, J.; Eiden, J.; Jansen, K.U., et al. The discovery and development of a novel vaccine to protect against Neisseria meningitidis serogroup B disease. Hum. Vaccines Immunother. 2015, 11, 5-13.
12. Serruto, D.; Bottomley, M.J.; Ram, S.; Giuliani, M.M.; Rappuoli, R. The new multicomponent vaccine against meningococcal serogroup B, 4CMenB: Immunological, functional and structural characterization of the antigens. Vaccine 2012, 30 (Suppl. 2), B87-B97.
13. Łyskowski, A.; Leo, J.C.; Goldman, A. Structure and Biology of Trimeric Autotransporter Adhesins; Springer: Dordrecht, The Netherlands, 2011; Volume 715, pp. 143-158.
14. Capecchi, B.; Adu-Bobie, J.; di Marcello, F.; Ciucchi, L.; Masignani, V.; Taddei, A.; Rappuoli, R.; Pizza, M.; Aricò, B.; Neisseria meningitidis NadA is a new invasin which promotes bacterial adhesion to and penetration into human epithelial cells. Mol. Microbiol. 2005, 55, 687-698.
15. Comanducci, M.; Bambini, S.; Brunelli, B.; Adu-Bobie, J.; Aricò, B.; Capecchi, B.; Giuliani, M.M.; Masignani, V.; Santini, L.; Savino, S., et al. NadA, a novel vaccine candidate of Neisseria meningitidis. J. Exp. Med. 2002, 195, 1445-1454.
16. Findlow, J.; Borrow, R.; Snape, M.D.; Dawson, T.; Holland, A.; John, T.M.; Evans, A.; Telford, K.L.; Ypma, E.; Toneatto, D., et al. Multicenter, open-label, randomized phase II controlled trial of an investigational recombinant meningococcal serogroup B vaccine with and without outer membrane vesicles, administered in infancy. Clin. Infect. Dis. 2010, 51, 1127-1137.
17. Bambini, S.; de Chiara, M.; Muzzi, A.; Mora, M.; Lucidarme, J.; Brehony, C.; Borrow, R.; Masignani, V.; Comanducci, M.; Maiden, M.C.J., et al. Neisseria adhesin a variation and revised nomenclature scheme. Clin. Vaccine Immunol. CVI 2014, 21, 966-971.
18. Dauter, Z. Solving coiled-coil protein structures. IUCrJ 2015, 2, 164-165.
19. Dupeux, F.; Rower, M.; Seroul, G.; Blot, D.; Marquez, J.A. A thermal stability assay can help to estimate the crystallization likelihood of biological samples. Acta Crystallogr. D 2011, 67, 915-919.
20. Malito, E.; Biancucci, M.; Faleri, A.; Ferlenghi, I.; Scarselli, M.; Maruggi, G.; Lo Surdo, P.; Veggi, D.; Liguori, A.; Santini, L., et al. Structure of the meningococcal vaccine antigen NadA and epitope mapping of a bactericidal antibody. Proc. Natl. Acad. Sci. USA 2014, 111, 17128-17133.
21. Dale, G.E.; Oefner, C.; D’Arcy, A. The protein as a variable in protein crystallization. J. Struct. Biol. 2003, 142, 88-97.
22. Keenan, R.J.; Siehl, D.L.; Gorton, R.; Castle, L.A. DNA shuffling as a tool for protein crystallization. Proc. Natl. Acad. Sci. USA 2005, 102, 8887-8892.
23. Hartmann, M.D.; Ridderbusch, O.; Zeth, K.; Albrecht, R.; Testa, O.; Woolfson, D.N.; Sauer, G.; Dunin-Horkawicz, S.; Lupas, A.N.; Alvarez, B.H. A coiled-coil motif that sequesters ions to the hydrophobic core. Proc. Natl. Acad. Sci. USA 2009, 106, 16950-16955.
24. Tavano, R.; Capecchi, B.; Montanari, P.; Franzoso, S.; Marin, O.; Sztukowska, M.; Cecchini, P.; Segat, D.; Scarselli, M.; Aricò, B., et al. Mapping of the Neisseria meningitidis NadA cell-binding site: Relevance of predicted α-helices in the NH2-terminal and dimeric coiled-coil regions. J. Bacteriol. 2011, 193, 107-115.
25. Berntsson, R.P.; Smits, S.H.; Schmitt, L.; Slotboom, D.J.; Poolman, B. A structural classification of substrate-binding proteins. FEBS Lett. 2010, 584, 2606-2617.
26. Bagnoli, F.; Fontana, M.R.; Soldaini, E.; Mishra, R.P.; Fiaschi, L.; Cartocci, E.; Nardi-Dei, V.; Ruggiero, P.; Nosari, S.; de Falco, M.G., et al. Vaccine composition formulated with a novel TLR7-dependent adjuvant induces high and broad protection against Staphylococcus aureus. Proc. Natl. Acad. Sci. USA 2015, 112, 3680-3685.
27. Mishra, R.P.; Mariotti, P.; Fiaschi, L.; Nosari, S.; Maccari, S.; Liberatori, S.; Fontana, M.R.; Pezzicoli, A.; de Falco, M.G.; Falugi, F., et al. Staphylococcus aureus FhuD2 is involved in the early phase of staphylococcal dissemination and generates protective immunity in mice. J. Infect. Dis. 2012, 206, 1041-1049.
28. Mariotti, P.; Malito, E.; Biancucci, M.; Lo Surdo, P.; Mishra, R.P.; Nardi-Dei, V.; Savino, S.; Nissum, M.; Spraggon, G.; Grandi, G., et al. Structural and functional characterization of the Staphylococcus aureus virulence factor and vaccine candidate FhuD2. Biochem. J. 2013, 449, 683-693.
29. Podkowa, K.J.; Briere, L.A.; Heinrichs, D.E.; Shilton, B.H. Crystal and solution structure analysis of FhuD2 from Staphylococcus aureus in multiple unliganded conformations and bound to ferrioxamine-B. Biochemistry 2014, 53, 2017-2031.
30. Scully, I.L.; Liberator, P.A.; Jansen, K.U.; Anderson, A.S. Covering all the bases: Preclinical development of an effective Staphylococcus aureus vaccine. Front. Immunol. 2014, 5, 109.
31. Abate, F.; Malito, E.; Cozzi, R.; Lo Surdo, P.; Maione, D.; Bottomley, M.J. Apo, Zn2+-bound and Mn2+-bound structures reveal ligand-binding properties of SitA from the pathogen Staphylococcus pseudintermedius. Biosci. Rep. 2014, 34, e00154, doi:10.1042/BSR20140088.
32. Gribenko, A.; Mosyak, L.; Ghosh, S.; Parris, K.; Svenson, K.; Moran, J.; Chu, L.; Li, S.; Liu, T.; Woods, V.L., Jr., et al. Three-dimensional structure and biophysical characterization of Staphylococcus aureus cell surface antigen-manganese transporter MntC. J. Mol. Biol. 2013, 425, 3429-3445.
33. Anderson, A.S.; Scully, I.L.; Timofeyeva, Y.; Murphy, E.; McNeil, L.K.; Mininni, T.; Nunez, L.; Carriere, M.; Singer, C.; Dilts, D.A., et al. Staphylococcus aureus manganese transport protein C is a highly conserved cell surface protein that elicits protective immunity against S. aureus and Staphylococcus epidermidis. J. Infect. Dis. 2012, 205, 1688-1696.
34. Ahuja, S.; Rouge, L.; Swem, D.L.; Sudhamsu, J.; Wu, P.; Russell, S.J.; Alexander, M.K.; Tam, C.; Nishiyama, M.; Starovasnik, M.A., et al. Structural analysis of bacterial ABC transporter inhibition by an antibody fragment. Structure 2015, 23, 713-723.
35. Plotkin, S.A.; Correlates of protection induced by vaccination. Clin. Vaccine Immunol. 2010, 17, 1055-1065.
36. Georgiou, G.; Ippolito, G.C.; Beausang, J.; Busse, C.E.; Wardemann, H.; Quake, S.R. The promise and challenge of high-throughput sequencing of the antibody repertoire. Nat. Biotechnol. 2014, 32, 158-168.
37. Huang, J.; Doria-Rose, N.A.; Longo, N.S.; Laub, L.; Lin, C.L.; Turk, E.; Kang, B.H.; Migueles, S.A.; Bailer, R.T.; Mascola, J.R., et al. Isolation of human monoclonal antibodies from peripheral blood B cells. Nat. Protoc. 2013, 8, 1907-1915.
38. Wilson, P.C.; Andrews, S.F. Tools to therapeutically harness the human antibody response. Nat. Rev. Immunol. 2012, 12, 709-719.
39. Donnarumma, D.; Bottomley, M.J.; Malito, E.; Settembre, E.; Ferlenghi, I.; Cozzi, R.; Advanced Vaccine Research; Bagnoli, F., Rappuoli, R., Eds.; Caister Academic Press: Norfolk, UK, 2015; pp. 103-132.
40. Malito, E.; Faleri, A.; Lo Surdo, P.; Veggi, D.; Maruggi, G.; Grassi, E.; Cartocci, E.; Bertoldi, I.; Genovese, A.; Santini, L., et al. Defining a protective epitope on factor H binding protein, a key meningococcal virulence factor and vaccine antigen. Proc. Natl. Acad. Sci. USA 2013, 110, 3304-3309.
41. Schneider, M.C.; Prosser, B.E.; Caesar, J.J.; Kugelberg, E.; Li, S.; Zhang, Q.; Quoraishi, S.; Lovett, J.E.; Deane, J.E.; Sim, R.B., et al. Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates. Nature 2009, 458, 890-893.
42. Giuntini, S.; Reason, D.C.; Granoff, D.M. Complement-mediated bactericidal activity of anti-factor H binding protein monoclonal antibodies against the meningococcus relies upon blocking factor H binding. Infect. Immun. 2011, 79, 3751-3759.
43. Chowdary, T.K.; Cairns, T.M.; Atanasiu, D.; Cohen, G.H.; Eisenberg, R.J.; Heldwein, E.E. Crystal structure of the conserved herpesvirus fusion regulator complex gH-gL. Nat. Struct. Mol. Biol. 2010, 17, 882-888.
44. Ciferri, C.; Chandramouli, S.; Donnarumma, D.; Nikitin, P.A.; Cianfrocco, M.A.; Gerrein, R.; Feire, A.L.; Barnett, S.W.; Lilja, A.E.; Rappuoli, R., et al. Structural and biochemical studies of HCMV gH/gL/gO and pentamer reveal mutually exclusive cell entry complexes. Proc. Natl. Acad. Sci. USA 2015, 112, 1767-1772.
45. Kringelum, J.V.; Nielsen, M.; Padkjaer, S.B.; Lund, O. Structural analysis of B-cell epitopes in antibody: Protein complexes. Mol. Immunol. 2013, 53, 24-34.
46. Griffin, L.; Lawson, A. Antibody fragments as tools in crystallography. Clin. Exp. Immunol. 2011, 165, 285-291.
47. Madico, G.; Welsch, J.A.; Lewis, L.A.; McNaughton, A.; Perlman, D.H.; Costello, C.E.; Ngampasutadol, J.; Vogel, U.; Granoff, D.M.; Ram, S. The meningococcal vaccine candidate GNA1870 binds the complement regulatory protein factor H and enhances serum resistance. J. Immunol. 2006, 177, 501-510.
48. Schneider, M.C.; Exley, R.M.; Chan, H.; Feavers, I.; Kang, Y.H.; Sim, R.B.; Tang, C.M. Functional significance of factor H binding to Neisseria meningitidis. J. Immunol. 2006, 176, 7566-7575.
49. Jolley, K.A.; Maiden, M.C. BIGSdb: Scalable analysis of bacterial genome variation at the population level. BMC Bioinform. 2010, 11, 595.
50. Giuliani, M.M.; Biolchi, A.; Serruto, D.; Ferlicca, F.; Vienken, K.; Oster, P.; Rappuoli, R.; Pizza, M.; Donnelly, J. Measuring antigen-specific bactericidal responses to a multicomponent vaccine against serogroup B meningococcus. Vaccine 2010, 28, 5023-5030.
51. Masignani, V.; Comanducci, M.; Giuliani, M.M.; Bambini, S.; Adu-Bobie, J.; Arico, B.; Brunelli, B.; Pieri, A.; Santini, L.; Savino, S., et al. Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870. J. Exp. Med. 2003, 197, 789-799.
52. Seib, K.L.; Serruto, D.; Oriente, F.; Delany, I.; Adu-Bobie, J.; Veggi, D.; Arico, B.; Rappuoli, R.; Pizza, M. Factor H-binding protein is important for meningococcal survival in human whole blood and serum and in the presence of the antimicrobial peptide LL-37. Infect. Immun. 2009, 77, 292-299.
53. Cantini, F.; Veggi, D.; Dragonetti, S.; Savino, S.; Scarselli, M.; Romagnoli, G.; Pizza, M.; Banci, L.; Rappuoli, R.; Solution structure of the factor H-binding protein, a survival factor and protective antigen of Neisseria meningitidis. J. Biol. Chem. 2009, 284, 9022-9026.
54. Cendron, L.; Veggi, D.; Girardi, E.; Zanotti, G. Structure of the uncomplexed Neisseria meningitides factor H-binding protein fHbp (rLP2086). Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 2011, 67, 531-535.
55. Mascioni, A.; Bentley, B.E.; Camarda, R.; Dilts, D.A.; Fink, P.; Gusarova, V.; Hoiseth, S.K.; Jacob, J.; Lin, S.L.; Malakian, K., et al. Structural basis for the immunogenic properties of the meningococcal vaccine candidate LP2086. J. Biol. Chem. 2009, 284, 8738-8746.
56. Johnson, S.; Tan, L.; van der Veen, S.; Caesar, J.; Goicoechea De Jorge, E.; Harding, R.J.; Bai, X.; Exley, R.M.; Ward, P.N.; Ruivo, N., et al. Design and evaluation of meningococcal vaccines through structure-based modification of host and pathogen molecules. PLoS Pathog. 2012, 8, e1002981.
57. Scarselli, M.; Arico, B.; Brunelli, B.; Savino, S.; di Marcello, F.; Palumbo, E.; Veggi, D.; Ciucchi, L.; Cartocci, E.; Bottomley, M.J., et al. Rational design of a meningococcal antigen inducing broad protective immunity. Sci. Transl. Med. 2011, 3, 91ra62, doi:10.1126/scitranslmed.3.91.91ra62.
58. Cozzi, R.; Scarselli, M.; Ferlenghi, I. Structural vaccinology: A three-dimensional view for vaccine development. Curr. Top. Med. Chem. 2013, 13, 2629-2637.
59. Dormitzer, P.R.; Grandi, G.; Rappuoli, R. Structural vaccinology starts to deliver. Nat. Rev. Microbiol. 2012, 10, 807-813.
60. Beernink, P.T.; Shaughnessy, J.; Ram, S.; Granoff, D.M. Impaired immunogenicity of a meningococcal factor H-binding protein vaccine engineered to eliminate factor h binding. Clin. Vaccine Immunol. 2010, 17, 1074-1078.
61. Beernink, P.T.; Shaughnessy, J.; Braga, E.M.; Liu, Q.; Rice, P.A.; Ram, S.; Granoff, D.M. A meningococcal factor H binding protein mutant that eliminates factor H binding enhances protective antibody responses to vaccination. J. Immunol. 2011, 186, 3606-3614.
62. Beernink, P.T.; Shaughnessy, J.; Pajon, R.; Braga, E.M.; Ram, S.; Granoff, D.M. The effect of human factor H on immunogenicity of meningococcal native outer membrane vesicle vaccines with over-expressed factor H binding protein. PLoS Pathog. 2012, 8, e1002688.
63. Van der Veen, S.; Johnson, S.; Jongerius, I.; Malik, T.; Genovese, A.; Santini, L.; Staunton, D.; Ufret-Vincenty, R.L.; Pickering, M.; Lea, S.M., et al. Non-functional variant 3 factor H binding proteins as meningococcal vaccine candidates. Infect. Immun. 2014, 82, 1157-1163.
64. Calmettes, C.; Alcantara, J.; Yu, R.H.; Schryvers, A.B.; Moraes, T.F. The structural basis of transferrin sequestration by transferrin-binding protein B. Nat. Struct. Mol. Biol. 2012, 19, 358-360.
65. Noinaj, N.; Buchanan, S.K.; Cornelissen, C.N. The transferrin-iron import system from pathogenic Neisseria species. Mol. Microbiol. 2012, 86, 246-257.
66. Noinaj, N.; Easley, N.C.; Oke, M.; Mizuno, N.; Gumbart, J.; Boura, E.; Steere, A.N.; Zak, O.; Aisen, P.; Tajkhorshid, E., et al. Structural basis for iron piracy by pathogenic Neisseria. Nature 2012, 483, 53-58.
67. Frandoloso, R.; Martinez-Martinez, S.; Calmettes, C.; Fegan, J.; Costa, E.; Curran, D.; Yu, R.H.; Gutierrez-Martin, C.B.; Rodriguez-Ferri, E.F.; Moraes, T.F., et al. Nonbinding site-directed mutants of transferrin binding protein B exhibit enhanced immunogenicity and protective capabilities. Infect. Immun. 2015, 83, 1030-1038.
68. Nair, H.; Nokes, D.J.; Gessner, B.D.; Dherani, M.; Madhi, S.A.; Singleton, R.J.; O’Brien, K.L.; Roca, A.; Wright, P.F.; Bruce, N., et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: A systematic review and meta-analysis. Lancet 2010, 375, 1545-1555.
69. Lozano, R.; Naghavi, M.; Foreman, K.; Lim, S.; Shibuya, K.; Aboyans, V.; Abraham, J.; Adair, T.; Aggarwal, R.; Ahn, S.Y., et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012, 380, 2095-2128.
70. Falsey, A.R.; Hennessey, P.A.; Formica, M.A.; Cox, C.; Walsh, E.E.; Respiratory syncytial virus infection in elderly and high-risk adults. N. Engl. J. Med. 2005, 352, 1749-1759.
71. The IMpact-RSV-Study-Group. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics 1998, 102, 531-537.
72. Guvenel, A.K.; Chiu, C.; Openshaw, P.J. Current concepts and progress in RSV vaccine development. Expert Rev. Vaccines 2014, 13, 333-344.
73. McCarthy, M.; Villafana, T.; Stillman, E.; Esser, M.T. Respiratory syncytial virus protein structure, function and implications for subunit vaccine development. Future Virol. 2014, 9, 753-767.
74. Anderson, R.; Huang, Y.; Langley, J.M. Prospects for defined epitope vaccines for respiratory syncytial virus. Future Microbiol. 2010, 5, 585-602.
75. McLellan, J.S.; Ray, W.C.; Peeples, M.E. Structure and function of respiratory syncytial virus surface glycoproteins. Curr. Top. Microbiol. Immunol. 2013, 372, 83-104.
76. Calder, L.J.; Gonzalez-Reyes, L.; Garcia-Barreno, B.; Wharton, S.A.; Skehel, J.J.; Wiley, D.C.; Melero, J.A. Electron microscopy of the human respiratory syncytial virus fusion protein and complexes that it forms with monoclonal antibodies. Virology 2000, 271, 122-131.
77. Liljeroos, L.; Krzyzaniak, M.A.; Helenius, A.; Butcher, S.J. Architecture of respiratory syncytial virus revealed by electron cryotomography. Proc. Natl. Acad. Sci. USA 2013, 110, 11133-11138.
78. Begona Ruiz-Arguello, M.; Gonzalez-Reyes, L.; Calder, L.J.; Palomo, C.; Martin, D.; Saiz, M.J.; Garcia-Barreno, B.; Skehel, J.J.; Melero, J.A. Effect of proteolytic processing at two distinct sites on shape and aggregation of an anchorless fusion protein of human respiratory syncytial virus and fate of the intervening segment. Virology 2002, 298, 317-326.
79. Swanson, K.A.; Settembre, E.C.; Shaw, C.A.; Dey, A.K.; Rappuoli, R.; Mandl, C.W.; Dormitzer, P.R.; Carfi, A. Structural basis for immunization with postfusion respiratory syncytial virus fusion F glycoprotein (RSV F) to elicit high neutralizing antibody titers. Proc. Natl. Acad. Sci. USA 2011, 108, 9619-9624.
80. Wu, H.; Pfarr, D.S.; Johnson, S.; Brewah, Y.A.; Woods, R.M.; Patel, N.K.; White, W.I.; Young, J.F.; Kiener, P.A.; Development of motavizumab, an ultra-potent antibody for the prevention of respiratory syncytial virus infection in the upper and lower respiratory tract. J. Mol. Biol. 2007, 368, 652-665.
81. McLellan, J.S.; Chen, M.; Chang, J.S.; Yang, Y.; Kim, A.; Graham, B.S.; Kwong, P.D. Structure of a major antigenic site on the respiratory syncytial virus fusion glycoprotein in complex with neutralizing antibody 101F. J. Virol. 2010, 84, 12236-12244.
82. McLellan, J.S.; Chen, M.; Kim, A.; Yang, Y.; Graham, B.S.; Kwong, P.D. Structural basis of respiratory syncytial virus neutralization by motavizumab. Nat. Struct. Mol. Biol. 2010, 17, 248-250.
83. McLellan, J.S.; Yang, Y.; Graham, B.S.; Kwong, P.D. Structure of respiratory syncytial virus fusion glycoprotein in the postfusion conformation reveals preservation of neutralizing epitopes. J. Virol. 2011, 85, 7788-7796.
84. Magro, M.; Mas, V.; Chappell, K.; Vazquez, M.; Cano, O.; Luque, D.; Terron, M.C.; Melero, J.A.; Palomo, C. Neutralizing antibodies against the preactive form of respiratory syncytial virus fusion protein offer unique possibilities for clinical intervention. Proc. Natl. Acad. Sci. USA 2012, 109, 3089-3094.
85. McLellan, J.S.; Chen, M.; Leung, S.; Graepel, K.W.; Du, X.; Yang, Y.; Zhou, T.; Baxa, U.; Yasuda, E.; Beaumont, T., et al. Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody. Science 2013, 340, 1113-1117.
86. McLellan, J.S.; Chen, M.; Joyce, M.G.; Sastry, M.; Stewart-Jones, G.B.; Yang, Y.; Zhang, B.; Chen, L.; Srivatsan, S.; Zheng, A., et al. Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. Science 2013, 342, 592-598.
87. McLellan, J.S.; Correia, B.E.; Chen, M.; Yang, Y.; Graham, B.S.; Schief, W.R.; Kwong, P.D. Design and characterization of epitope-scaffold immunogens that present the motavizumab epitope from respiratory syncytial virus. J. Mol. Biol. 2011, 409, 853-866.
88. Correia, B.E.; Bates, J.T.; Loomis, R.J.; Baneyx, G.; Carrico, C.; Jardine, J.G.; Rupert, P.; Correnti, C.; Kalyuzhniy, O.; Vittal, V., et al. Proof of principle for epitope-focused vaccine design. Nature 2014, 507, 201-206.
89. Koff, W.C.; Russell, N.D.; Walport, M.; Feinberg, M.B.; Shiver, J.W.; Karim, S.A.; Walker, B.D.; McGlynn, M.G.; Nweneka, C.V.; Nabel, G.J.; Accelerating the development of a safe and effective HIV vaccine: HIV vaccine case study for the Decade of Vaccines. Vaccine 2013, 31 (Suppl. 2), B204-B208.
90. Ward, A.B.; Wilson, I.A. Insights into the trimeric HIV-1 envelope glycoprotein structure. Trends Biochem. Sci. 2015, 40, 101-107.
91. Rerks-Ngarm, S.; Pitisuttithum, P.; Nitayaphan, S.; Kaewkungwal, J.; Chiu, J.; Paris, R.; Premsri, N.; Namwat, C.; de Souza, M.; Adams, E., et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N. Engl. J. Med. 2009, 361, 2209-2220.
92. Haynes, B.F.; Gilbert, P.B.; McElrath, M.J.; Zolla-Pazner, S.; Tomaras, G.D.; Alam, S.M.; Evans, D.T.; Montefiori, D.C.; Karnasuta, C.; Sutthent, R., et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N. Engl. J. Med. 2012, 366, 1275-1286.
93. West, A.P., Jr.; Scharf, L.; Scheid, J.F.; Klein, F.; Bjorkman, P.J.; Nussenzweig, M.C. Structural insights on the role of antibodies in HIV-1 vaccine and therapy. Cell 2014, 156, 633-648.
94. Kwong, P.D.; Mascola, J.R.; Nabel, G.J. Broadly neutralizing antibodies and the search for an HIV-1 vaccine: The end of the beginning. Nat. Rev. Immunol. 2013, 13, 693-701.
95. Kwong, P.D.; Wyatt, R.; Robinson, J.; Sweet, R.W.; Sodroski, J.; Hendrickson, W.A. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 1998, 393, 648-659.
96. Correia, B.E.; Ban, Y.E.; Holmes, M.A.; Xu, H.; Ellingson, K.; Kraft, Z.; Carrico, C.; Boni, E.; Sather, D.N.; Zenobia, C., et al. Computational design of epitope-scaffolds allows induction of antibodies specific for a poorly immunogenic HIV vaccine epitope. Structure 2010, 18, 1116-1126.
97. Azoitei, M.L.; Correia, B.E.; Ban, Y.-E.A.; Carrico, C.; Kalyuzhniy, O.; Chen, L.; Schroeter, A.; Huang, P.-S.; Mclellan, J.S.; Kwong, P.D., et al. Computation-guided backbone grafting of a discontinuous motif onto a protein scaffold. Science 2011, 334, 373-376.
98. Ofek, G.; Guenaga, F.J.; Schief, W.R.; Skinner, J.; Baker, D.; Wyatt, R.; Kwong, P.D. Elicitation of structure-specific antibodies by epitope scaffolds. Proc. Natl. Acad. Sci. USA 2010, 107, 17880-17887.
99. Dey, B.; Svehla, K.; Xu, L.; Wycuff, D.; Zhou, T.; Voss, G.; Phogat, A.; Chakrabarti, B.K.; Li, Y.; Shaw, G., et al. Structure-based stabilization of HIV-1 gp120 enhances humoral immune responses to the induced co-receptor binding site. PLoS Pathog. 2009, 5, e1000445.
100. Kassa, A.; Dey, A.K.; Sarkar, P.; Labranche, C.; Go, E.P.; Clark, D.F.; Sun, Y.; Nandi, A.; Hartog, K.; Desaire, H., et al. Stabilizing exposure of conserved epitopes by structure guided insertion of disulfide bond in HIV-1 envelope glycoprotein. PLoS ONE 2013, 8, e76139.
101. Jardine, J.; Julien, J.P.; Menis, S.; Ota, T.; Kalyuzhniy, O.; McGuire, A.; Sok, D.; Huang, P.S.; MacPherson, S.; Jones, M., et al. Rational HIV immunogen design to target specific germline B cell receptors. Science 2013, 340, 711-716.
102. Julien, J.P.; Cupo, A.; Sok, D.; Stanfield, R.L.; Lyumkis, D.; Deller, M.C.; Klasse, P.J.; Burton, D.R.; Sanders, R.W.; Moore, J.P., et al. Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science 2013, 342, 1477-1483.
103. Pancera, M.; Zhou, T.; Druz, A.; Georgiev, I.S.; Soto, C.; Gorman, J.; Huang, J.; Acharya, P.; Chuang, G.Y.; Ofek, G., et al. Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature 2014, 514, 455-461.
104. Lyumkis, D.; Julien, J.P.; de Val, N.; Cupo, A.; Potter, C.S.; Klasse, P.J.; Burton, D.R.; Sanders, R.W.; Moore, J.P.; Carragher, B., et al. Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science 2013, 342, 1484-1490.
105. Sanders, R.W.; Derking, R.; Cupo, A.; Julien, J.P.; Yasmeen, A.; de Val, N.; Kim, H.J.; Blattner, C.; de la Pena, A.T.; Korzun, J., et al. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. PLoS Pathog. 2013, 9, e1003618.
106. Hol, W.; Verlinde, C.; Macromolecular Crystallography and Medicine; Springer: Dordrecht, UK; Boston, UK; London, UK, 2006; Volume F, pp. 10-25.
107. Tickle, I.; Sharff, A.; Vinkovic, M.; Yon, J.; Jhoti, H. High-throughput protein crystallography and drug discovery. Chem. Soc. Rev. 2004, 33, 558-565.
108. Berman, H.M.; Kleywegt, G.J.; Nakamura, H.; Markley, J.L. The protein data bank at 40: Reflecting on the past to prepare for the future. Structure (Lond., Engl.) 2012, 20, 391-396.
109. Terwilliger, T.C.; Stuart, D.; Yokoyama, S. Lessons from structural genomics. Ann. Rev. Biophys. 2009, 38, 371-383.
110. Bernal, J.D.; Crowfoot, D. X-ray photographs of crystalline pepsin. Nature 1934, 133, 794-795.
111. Kendrew, J.C.; Bodo, G.; Dintzis, H.M.; Parrish, R.G.; Wyckoff, H.; Phillips, D.C. A three-dimensional model of the myoglobin molecule obtained by X-ray analysis. Nature 1958, 181, 662-666.
112. Kendrew, J.C.; Dickerson, R.E.; Strandberg, B.E.; Hart, R.G.; Davies, D.R.; Phillips, D.C.; Shore, V.C. Structure of myoglobin: A three-dimensional Fourier synthesis at 2 Å. resolution. Nature 1960, 185, 422-427.
113. Perutz, M.F.; Rossmann, M.G.; Cullis, A.F.; Muirhead, H.; Will, G.; North, A.C. Structure of haemoglobin: A three-dimensional Fourier synthesis at 5.5-A. resolution, obtained by X-ray analysis. Nature 1960, 185, 416-422.
114. Blake, C.C.; Fenn, R.H.; North, A.C.; Phillips, D.C.; Poljak, R.J. Structure of lysozyme. A Fourier map of the electron density at 6 angstrom resolution obtained by X-ray diffraction. Nature 1962, 196, 1173-1176.
115. Blake, C.C.; Koenig, D.F.; Mair, G.A.; North, A.C.; Phillips, D.C.; Sarma, V.R. Structure of hen egg-white lysozyme. A three-dimensional Fourier synthesis at 2 Angstrom resolution. Nature 1965, 206, 757-761.
116. Garman, E.F. Developments in X-ray crystallographic structure determination of biological macromolecules. Science 2014, 343, 1102-1108.
117. Chayen, N.E.; Saridakis, E. Protein crystallization: From purified protein to diffraction-quality crystal. Nat. Methods 2008, 5, 147-153.
118. Bukowska, M.A.; Grütter, M.G. New concepts and aids to facilitate crystallization. Curr. Opin. Struct. Biol. 2013, 23, 409-416.
119. McPherson, A.; Cudney, B. Optimization of crystallization conditions for biological macromolecules. Acta Crystallogr. Sect. F Struct. Biol. Commun. 2014, 70, 1445-1467.
120. Chandonia, J.-M.; Brenner, S.E. The impact of structural genomics: Expectations and outcomes. Science 2006, 311, 347-351.
121. Hendrickson, W.A.; Impact of structures from the protein structure initiative. Structure (Lond., Engl.) 2007, 15, 1528-1529.
122. Rupp, B.; High-throughput crystallography at an affordable cost: The TB structural genomics consortium crystallization facility. Acc. Chem. Res. 2003, 36, 173-181.
123. Vedadi, M.; Arrowsmith, C.H.; Allali-Hassani, A.; Senisterra, G.; Wasney, G.A. Biophysical characterization of recombinant proteins: A key to higher structural genomics success. J. Struct. Biol. 2010, 172, 107-119.
124. Yumerefendi, H.; Tarendeau, F.; Mas, P.J.; Hart, D.J. ESPRIT: An automated, library-based method for mapping and soluble expression of protein domains from challenging targets. J. Struct. Biol. 2010, 172, 66-74.
125. Reich, S.; Puckey, L.H.; Cheetham, C.L.; Harris, R.; Ali, A.A.; Bhattacharyya, U.; Maclagan, K.; Powell, K.A.; Prodromou, C.; Pearl, L.H., et al. Combinatorial domain hunting: An effective approach for the identification of soluble protein domains adaptable to high-throughput applications. Protein Sci. 2006, 15, 2356-2365.
126. Derewenda, Z.S.; Application of protein engineering to enhance crystallizability and improve crystal properties. Acta Crystallogr. D 2010, 66, 604-615.
127. Lamazares, E.; Clemente, I.; Bueno, M.; Velazquez-Campoy, A.; Sancho, J. Rational stabilization of complex proteins: A divide and combine approach. Sci. Rep. 2015, 5, 9129.
128. Derewenda, Z.S.; Vekilov, P.G. Entropy and surface engineering in protein crystallization. Acta Crystallogr. D 2006, 62, 116-124.
129. Zou, Y.; Weis, W.I.; Kobilka, B.K. N-terminal T4 lysozyme fusion facilitates crystallization of a G protein coupled receptor. PLoS ONE 2012, 7, e46039.
130. Chun, E.; Thompson, A.A.; Liu, W.; Roth, C.B.; Griffith, M.T.; Katritch, V.; Kunken, J.; Xu, F.; Cherezov, V.; Hanson, M.A., et al. Fusion partner toolchest for the stabilization and crystallization of G protein-coupled receptors. Structure 2012, 20, 967-976.
131. Hassell, A.M.; An, G.; Bledsoe, R.K.; Bynum, J.M.; Carter, H.L.; Deng, S.-J.J.; Gampe, R.T.; Grisard, T.E.; Madauss, K.P.; Nolte, R.T., et al. Crystallization of protein-ligand complexes. Acta Crystallogr. D 2007, 63, 72-79.
132. Tereshko, V.; Uysal, S.; Koide, A.; Margalef, K.; Koide, S.; Kossiakoff, A.A. Toward chaperone-assisted crystallography: Protein engineering enhancement of crystal packing and X-ray phasing capabilities of a camelid single-domain antibody (VHH) scaffold. Protein Sci. Publ. Protein Soc. 2008, 17, 1175-1187.
133. Wernimont, A.; Edwards, A. In situ proteolysis to generate crystals for structure determination: An update. PLoS ONE 2009, 4, e5094.
134. D’Arcy, A.; Villard, F.; Marsh, M. An automated microseed matrix-screening method for protein crystallization. Acta crystallogr. Sect. D Biol. Crystallogr. 2007, 63, 550-554.
135. Bergfors, T. Seeds to crystals. J. Struct. Biol. 2003, 142, 66-76.
136. Walter, T.S.; Meier, C.; Assenberg, R.; Au, K.-F.; Ren, J.; Verma, A.; Nettleship, J.E.; Owens, R.J.; Stuart, D.I.; Grimes, J.M. Lysine methylation as a routine rescue strategy for protein crystallization. Structure (Lond., Engl.) 2006, 14, 1617-1622.
137. Kim, Y.; Quartey, P.; Li, H.; Volkart, L.; Hatzos, C.; Chang, C.; Nocek, B.; Cuff, M.; Osipiuk, J.; Tan, K., et al. Large-scale evaluation of protein reductive methylation for improving protein crystallization. Nat. Methods 2008, 5, 853-854.
138. Newman, J.; Bolton, E.E.; Mueller-Dieckmann, J.; Fazio, V.J.; Gallagher, D.T.; Lovell, D.; Luft, J.R.; Peat, T.S.; Ratcliffe, D.; Sayle, R.A., et al. On the need for an international effort to capture, share and use crystallization screening data. Acta Crystallogr. F 2012, 68, 253-258
139. Fazio, V.J.; Peat, T.S.; Newman, J. A drunken search in crystallization space. Acta Crystallogr. F 2014, 70, 1303-1311.
140. Fusco, D.; Barnum, T.J.; Bruno, A.E.; Luft, J.R.; Snell, E.H.; Mukherjee, S.; Charbonneau, P. Statistical analysis of crystallization database links protein physico-chemical features with crystallization mechanisms. PLoS ONE 2014, 9, e101123.
141. Ng, J.T.; Dekker, C.; Kroemer, M.; Osborne, M.; von Delft, F. Using textons to rank crystallization droplets by the likely presence of crystals. Acta Crystallogr. D 2014, 70, 2702-2718.
142. Dauter, Z.; Jaskolski, M.; Wlodawer, A. Impact of synchrotron radiation on macromolecular crystallography: A personal view. J. Synchrotron Radiat. 2010, 17, 433-444.
143. Broennimann, C.; Eikenberry, E.F.; Henrich, B.; Horisberger, R.; Huelsen, G.; Pohl, E.; Schmitt, B.; Schulze-Briese, C.; Suzuki, M.; Tomizaki, T., et al. The PILATUS 1M detector. J. Synchrotron Radiat. 2006, 13, 120-130.
144. Mueller, M.; Wang, M.; Schulze-Briese, C. Optimal fine φ-slicing for single-photon-counting pixel detectors. Acta Crystallogr. D 2012, 68, 42-56.
145. Gabadinho, J.; Beteva, A.; Guijarro, M.; Rey-Bakaikoa, V.; Spruce, D.; Bowler, M.W.; Brockhauser, S.; Flot, D.; Gordon, E.J.; Hall, D.R., et al. MxCuBE: A synchrotron beamline control environment customized for macromolecular crystallography experiments. J. Synchrotron Radiat. 2010, 17, 700-707.
146. Helliwell, J.R.; Mitchell, E.P. Synchrotron radiation macromolecular crystallography: Science and spin-offs. IUCrJ 2015, 2, 283-291.
147. Malbet-Monaco, S.; Leonard, G.A.; Mitchell, E.P.; Gordon, E.J.; How the ESRF helps industry and how they help the ESRF. Acta Crystallogr. D 2013, 69, 1289-1296.
148. Schlichting, I. Serial femtosecond crystallography: The first five years. IUCrJ 2015, 2, 246-255.
149. Boutet, S.; Lomb, L.; Williams, G.J.; Barends, T.R.; Aquila, A.; Doak, R.B.; Weierstall, U.; DePonte, D.P.; Steinbrener, J.; Shoeman, R.L., et al. High-resolution protein structure determination by serial femtosecond crystallography. Science 2012, 337, 362-364.
150. Liu, W.; Wacker, D.; Gati, C.; Han, G.W.; James, D.; Wang, D.; Nelson, G.; Weierstall, U.; Katritch, V.; Barty, A., et al. Serial femtosecond crystallography of G protein-coupled receptors. Science 2013, 342, 1521-1524.
151. Tenboer, J.; Basu, S.; Zatsepin, N.; Pande, K.; Milathianaki, D.; Frank, M.; Hunter, M.; Boutet, S.; Williams, G.J.; Koglin, J.E., et al. Time-resolved serial crystallography captures high-resolution intermediates of photoactive yellow protein. Science 2014, 346, 1242-1246.
152. Hendrickson, W.A. Determination of macromolecular structures from anomalous diffraction of synchrotron radiation. Science 1991, 254, 51-58.
153. Garman, E.; Murray, J.W. Heavy-atom derivatization. Acta Crystallogr. D 2003, 59, 1903-1913.
154. Rould, M.A. The same but different: Isomorphous methods for phasing and high-throughput ligand screening. Methods Mol. Biol. 2007, 364, 159-182.
155. Gonzalez, A.; von Delft, F.; Liddington, R.C.; Bakolitsa, C. Two-wavelength MAD phasing and radiation damage: A case study. J. Synchrotron Radiat. 2005, 12, 285-291.
156. Dodson, E. Is it jolly SAD? Acta Crystallogr. Sect. D Biol. Crystallogr. 2003, 59, 1958-1965.
157. Dauter, Z. One-and-a-half wavelength approach. Acta Crystallogr. D 2002, 58, 1958-1967.
158. Abendroth, J.; Gardberg, A.S.; Robinson, J.I.; Christensen, J.S.; Staker, B.L.; Myler, P.J.; Stewart, L.J.; Edwards, T.E. SAD phasing using iodide ions in a high-throughput structural genomics environment. J. Struct. Funct. Genomics 2011, 12, 83-95.
159. Dauter, Z. New approaches to high-throughput phasing. Curr. Opin. Struct. Biol. 2002, 12, 674-678.
160. Dauter, Z.; Li, M.; Wlodawer, A. Practical experience with the use of halides for phasing macromolecular structures: A powerful tool for structural genomics. Acta Crystallogr. D 2001, 57, 239-249.
161. Nagem, R.A.; Dauter, Z.; Polikarpov, I.; Protein crystal structure solution by fast incorporation of negatively and positively charged anomalous scatterers. Acta Crystallogr. D 2001, 57, 996-1002.
162. Scapin, G. Molecular replacement then and now. Acta Crystallogr. D 2013, 69, 2266-2275.
163. Evans, P.; McCoy, A. An introduction to molecular replacement. Acta Crystallogr. D 2008, 64, 1-10.
164. Abergel, C. Molecular replacement: Tricks and treats. Acta Crystallogr. D 2013, 69 Pt 11, 2167-2173.
165. McCoy, A.J.; Grosse-Kunstleve, R.W.; Adams, P.D.; Winn, M.D.; Storoni, L.C.; Read, R.J. Phaser crystallographic software. J. Appl. Crystallogr. 2007, 40, 658-674.
166. Vagin, A.; Teplyakov, A. MOLREP: An automated program for molecular replacement. J. Appl. Crystallogr. 1997, 30, 1022-1025.
167. Long, F.; Vagin, A.A.; Young, P.; Murshudov, G.N. BALBES: A molecular-replacement pipeline. Acta Crystallogr. Sect. D Biol. Crystallogr. 2008, 64, 125-132.
168. Keegan, R.M.; Winn, M.D. MrBUMP: An automated pipeline for molecular replacement. Acta Crystallogr. Sect. D Biol. Crystallogr. 2008, 64, 119-124.
169. Stokes-Rees, I.; Sliz, P. Protein structure determination by exhaustive search of Protein Data Bank derived databases. Proc. Natl. Acad. Sci. USA 2010, 107, 21476-21481.
170. Afonine, P.V.; Grosse-Kunstleve, R.W.; Echols, N.; Headd, J.J.; Moriarty, N.W.; Mustyakimov, M.; Terwilliger, T.C.; Urzhumtsev, A.; Zwart, P.H.; Adams, P.D. Towards automated crystallographic structure refinement with phenix.refine. Acta Crystallogr. D 2012, 68, 352-367.
171. Winn, M.D.; Ballard, C.C.; Cowtan, K.D.; Dodson, E.J.; Emsley, P.; Evans, P.R.; Keegan, R.M.; Krissinel, E.B.; Leslie, A.G.; McCoy, A., et al. Overview of the CCP4 suite and current developments. Acta Crystallogr. Sect. D Biol. Crystallogr. 2011, 67, 235-242.
172. Morin, A.; Eisenbraun, B.; Key, J.; Sanschagrin, P.C.; Timony, M.A.; Ottaviano, M.; Sliz, P. Collaboration gets the most out of software. eLife 2013, 2, e01456.
173. Aoki, S.T.; Settembre, E.C.; Trask, S.D.; Greenberg, H.B.; Harrison, S.C.; Dormitzer, P.R. Structure of rotavirus outer-layer protein VP7 bound with a neutralizing Fab. Science 2009, 324, 1444-1447.
174. Li, X.; Mooney, P.; Zheng, S.; Booth, C.R.; Braunfeld, M.B.; Gubbens, S.; Agard, D.A.; Cheng, Y. Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM. Nat. Methods 2013, 10, 584-590.
175. Zhang, X.; Settembre, E.; Xu, C.; Dormitzer, P.R.; Bellamy, R.; Harrison, S.C.; Grigorieff, N. Near-atomic resolution using electron cryomicroscopy and single-particle reconstruction. Proc. Natl. Acad. Sci. USA 2008, 105, 1867-1872.
176. Brown, A.; Amunts, A.; Bai, X.C.; Sugimoto, Y.; Edwards, P.C.; Murshudov, G.; Scheres, S.H.; Ramakrishnan, V. Structure of the large ribosomal subunit from human mitochondria. Science 2014, 346, 718-722.
177. Liao, M.; Cao, E.; Julius, D.; Cheng, Y. Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 2013, 504, 107-112.
178. Wu, S.; Avila-Sakar, A.; Kim, J.; Booth, D.S.; Greenberg, C.H.; Rossi, A.; Liao, M.; Li, X.; Alian, A.; Griner, S.L., et al. Fabs enable single particle cryoEM studies of small proteins. Structure 2012, 20, 582-592.
179. Zhang, Q.; Noble, K.A.; Mao, Y.; Young, N.L.; Sathe, S.K.; Roux, K.H.; Marshall, A.G. Rapid screening for potential epitopes reactive with a polycolonal antibody by solution-phase H/D exchange monitored by FT-ICR mass spectrometry. J. Am. Soc. Mass Spectrom. 2013, 24, 1016-1025.
180. Landgraf, R.R.; Chalmers, M.J.; Griffin, P.R. Automated hydrogen/deuterium exchange electron transfer dissociation high resolution mass spectrometry measured at single-amide resolution. J. Am. Soc. Mass Spectrom. 2012, 23, 301-309.