Structural insights into the extracellular recognition of the human serotonin 2B receptor by an antibody

Proceedings of the National Academy of Sciences of the United States of America

Volumn 114, Issue 31, 2017, Pages 8223-8228

  Ishchenko, Andrii ^a   Wacker, Daniel ^b   Kapoor, Mili ^c,g   Zhang, Ai ^c   Han, Gye Won ^a   Basu, Shibom ^d,h   Patel, Nilkanth ^a   Messerschmidt, Marc ^e   Weierstall, Uwe ^d   Liu, Wei ^d   Katritch, Vsevolod ^a   Roth, Bryan L ^b,f   Stevens, Raymond C ^a   Cherezov, Vadim ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^c SCRIPPS RESEARCH INSTITUTE   (United States)

^d ARIZONA STATE UNIVERSITY   (United States)

^e BioXFEL Science and Technology Center   (United States)

^f University of North Carolina   (United States)

^g Amplyx Pharmaceuticals   (United States)

^h PAUL SCHERRER INSTITUTE   (Switzerland)

Author keywords

Active state; Antibody recognition; GPCR; Serial femtosecond crystallography; X ray free electron laser

Indexed keywords

ERGOTAMINE; IMMUNOGLOBULIN F(AB) FRAGMENT; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY P2C2; SEROTONIN 2B RECEPTOR; UNCLASSIFIED DRUG; EPITOPE; SEROTONIN AGONIST;

AMINO TERMINAL SEQUENCE; ANIMAL CELL; ANTIGEN BINDING; ARTICLE; BINDING AFFINITY; CARBOXY TERMINAL SEQUENCE; COMPLEMENTARITY DETERMINING REGION; COMPLEX FORMATION; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; CRYSTALLIZATION; EXTRACELLULAR MATRIX; FEMALE; FEMTOSECOND LASER; HYDROGEN BOND; LIPID MEMBRANE; MOLECULAR RECOGNITION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN EXPRESSION; PROTEIN MOTIF; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; X RAY CRYSTALLOGRAPHY; BINDING COMPETITION; CHEMISTRY; ENZYME ACTIVE SITE; HUMAN; IMMUNOLOGY; METABOLISM; MOLECULAR MODEL;

ANTIBODIES, MONOCLONAL; BINDING, COMPETITIVE; CATALYTIC DOMAIN; CRYSTALLOGRAPHY, X-RAY; EPITOPES; ERGOTAMINE; HUMANS; IMMUNOGLOBULIN FAB FRAGMENTS; MODELS, MOLECULAR; PROTEIN CONFORMATION; RECEPTOR, SEROTONIN, 5-HT2B; SEROTONIN RECEPTOR AGONISTS;

EID: 85026770347     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1700891114     Document Type: Article

References (39)

1. Golay J, Introna M (2012) Mechanism of action of therapeutic monoclonal antibodies: Promises and pitfalls of in vitro and in vivo assays. Arch Biochem Biophys 526:146–153.
2. Hutchings CJ, Koglin M, Marshall FH (2010) Therapeutic antibodies directed at G protein-coupled receptors. MAbs 2:594–606.
3. Blanpain C, et al. (2002) Multiple active states and oligomerization of CCR5 revealed by functional properties of monoclonal antibodies. Mol Biol Cell 13:723–737.
4. Baribaud F, et al. (2001) Antigenically distinct conformations of CXCR4. J Virol 75: 8957–8967.
5. Babcock GJ, Mirzabekov T, Wojtowicz W, Sodroski J (2001) Ligand binding characteristics of CXCR4 incorporated into paramagnetic proteoliposomes. J Biol Chem 276: 38433–38440.
6. Jähnichen S, et al. (2010) CXCR4 nanobodies (VHH-based single variable domains) potently inhibit chemotaxis and HIV-1 replication and mobilize stem cells. Proc Natl Acad Sci USA 107:20565–20570.
7. O’Connor KH, et al. (2005) Requirement of multiple phage displayed peptide libraries for optimal mapping of a conformational antibody epitope on CCR5. J Immunol Methods 299:21–35.
8. Mancia F, et al. (2007) Production and characterization of monoclonal antibodies sensitive to conformation in the 5HT2c serotonin receptor. Proc Natl Acad Sci USA 104:4303–4308.
9. Gupta A, Heimann AS, Gomes I, Devi LA (2008) Antibodies against G-protein coupled receptors: Novel uses in screening and drug development. Comb Chem High Throughput Screen 11:463–467.
10. Yamamoto K, et al. (2010) Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma. J Clin Oncol 28:1591–1598.
11. Webb DR, Handel TM, Kretz-Rommel A, Stevens RC (2013) Opportunities for functional selectivity in GPCR antibodies. Biochem Pharmacol 85:147–152.
12. Jo M, Jung ST (2016) Engineering therapeutic antibodies targeting G-protein-coupled receptors. Exp Mol Med 48:e207.
13. Rasmussen SGF, et al. (2011) Crystal structure of the ß2 adrenergic receptor-Gs protein complex. Nature 477:549–555.
14. Hino T, et al. (2012) G-protein-coupled receptor inactivation by an allosteric inverse-agonist antibody. Nature 482:237–240.
15. Rasmussen SGF, et al. (2007) Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. Nature 450:383–387.
16. Kruse AC, et al. (2013) Activation and allosteric modulation of a muscarinic acetyl-choline receptor. Nature 504:101–106.
17. Huang W, et al. (2015) Structural insights into µ-opioid receptor activation. Nature 524:315–321.
18. Wacker D, et al. (2013) Structural features for functional selectivity at serotonin receptors. Science 340:615–619.
19. Liu W, et al. (2013) Serial femtosecond crystallography of G protein-coupled receptors. Science 342:1521–1524.
20. Wacker D, et al. (2017) Crystal structure of an LSD-bound human serotonin receptor. Cell 168:377–389.e12.
21. Xu F, et al. (2011) Structure of an agonist-bound human A2A adenosine receptor. Science 332:322–327.
22. Kang Y, et al. (2015) Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature 523:561–567.
23. Carpenter B, Nehmé R, Warne T, Leslie AGW, Tate CG (2016) Structure of the adenosine A(2A) receptor bound to an engineered G protein. Nature 536:104–107.
24. Xiang J, et al. (2016) Successful strategies to determine high-resolution structures of GPCRs. Trends Pharmacol Sci 37:1055–1069.
25. Katritch V, Cherezov V, Stevens RC (2013) Structure-function of the G protein-coupled receptor superfamily. Annu Rev Pharmacol Toxicol 53:531–556.
26. Valentin-Hansen L, Holst B, Frimurer TM, Schwartz TW (2012) PheVI:09 (Phe6.44) as a sliding microswitch in seven-transmembrane (7TM) G protein-coupled receptor activation. J Biol Chem 287:43516–43526.
27. Rasmussen SGF, et al. (2011) Structure of a nanobody-stabilized active state of the ß(2) adrenoceptor. Nature 469:175–180.
28. Setola V, Roth BL (2005) Screening the receptorome reveals molecular targets responsible for drug-induced side effects: Focus on ‘fen-phen’. Expert Opin Drug Metab Toxicol 1:377–387.
29. Kroeze WK, et al. (2015) PRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome. Nat Struct Mol Biol 22:362–369.
30. Caffrey M, Cherezov V (2009) Crystallizing membrane proteins using lipidic meso-phases. Nat Protoc 4:706–731.
31. Cheng A, Hummel B, Qiu H, Caffrey M (1998) A simple mechanical mixer for small viscous lipid-containing samples. Chem Phys Lipids 95:11–21.
32. Liu W, Ishchenko A, Cherezov V (2014) Preparation of microcrystals in lipidic cubic phase for serial femtosecond crystallography. Nat Protoc 9:2123–2134.
33. Barty A, et al. (2014) Cheetah: Software for high-throughput reduction and analysis of serial femtosecond X-ray diffraction data. J Appl Cryst 47:1118–1131.
34. White TA, et al. (2012) CrystFEL: A software suite for snapshot serial crystallography. J Appl Cryst 45:335–341.
35. McCoy AJ, et al. (2007) Phaser crystallographic software. J Appl Cryst 40:658–674.
36. Zwart PH, et al. (2008) Automated structure solution with the PHENIX suite. Methods Mol Biol 426:419–435.
37. Emsley P, Cowtan K (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60:2126–2132.
38. Adams PD, et al. (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66:213–221.
39. Smart OS, et al. (2012) Exploiting structure similarity in refinement: Automated NCS and target-structure restraints in BUSTER. Acta Crystallogr D Biol Crystallogr 68: 368–380.