Dynamic Cholesterol-Conditioned Dimerization of the G Protein Coupled Chemokine Receptor Type 4

PLoS Computational Biology

Volumn 12, Issue 11, 2016, Pages

  Pluhackova, Kristyna ^a   Gahbauer, Stefan ^a   Kranz, Franziska ^a   Wassenaar, Tsjerk A ^a,b   Böckmann, Rainer A ^a  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^b UNIVERSITY OF GRONINGEN   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MEMBRANES; CYTOLOGY; DIMERIZATION; DIMERS; MOLECULAR DYNAMICS; PHOSPHOLIPIDS; PROTEINS;

CHEMOKINE RECEPTORS; DIMER MOTIFS; DIMERIZATIONS; DYNAMICS SIMULATION; G PROTEIN; G PROTEIN COUPLED RECEPTORS; MEMBRANE CHOLESTEROL; PHOSPHOLIPID MEMBRANE; PHOSPHOLIPIDS BILAYER; TRANSMEMBRANE HELIX;

CHOLESTEROL;

CHEMOKINE RECEPTOR CXCR4; CHOLESTEROL; DIMER; CXCR4 PROTEIN, HUMAN; G PROTEIN COUPLED RECEPTOR; PROTEIN BINDING;

ARTICLE; BINDING SITE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DIMERIZATION; MEMBRANE COMPONENT; MOLECULAR DYNAMICS; PHOSPHOLIPID BILAYER; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN LIPID INTERACTION; PROTEIN MOTIF; RECEPTOR BINDING; CHEMICAL MODEL; CHEMISTRY; COMPUTER SIMULATION; KINETICS; LIPID BILAYER; PROTEIN CONFORMATION; PROTEIN MULTIMERIZATION; STRUCTURE ACTIVITY RELATION; ULTRASTRUCTURE;

BINDING SITES; CHOLESTEROL; COMPUTER SIMULATION; KINETICS; LIPID BILAYERS; MODELS, CHEMICAL; MOLECULAR DYNAMICS SIMULATION; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN MULTIMERIZATION; RECEPTORS, CXCR4; RECEPTORS, G-PROTEIN-COUPLED; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84999683667     PISSN: 1553734X     EISSN: 15537358     Source Type: Journal    
DOI: 10.1371/journal.pcbi.1005169     Document Type: Article

References (67)

1. Prezeau L, Rives ML, Comps-Agrar L, Maurel D, Kniazeff J, Pin JP, Functional crosstalk between GPCRs: with or without oligomerization. Curr Op Pharm. 2010;10:6–13. doi: 10.1016/j.coph.2009.10.009
2. Han Y, Moreira IS, Urizar E, Weinstein H, Javitch JA, Allosteric communication between protomers of dopamine class A GPCR dimers modulates activation. Nat Chem Biol. 2009;5:688–695. doi: 10.1038/nchembio.19919648932
3. Maurice P, Kamal M, Jockers R, Asymmetry of GPCR oligomers supports their functional relevance. Trends Pharmacol Sci. 2011;32:514–520. doi: 10.1016/j.tips.2011.05.00621715028
4. Kniazeff J, Prezeau L, Rondard P, Pin JP, Goudet C, Dimers and beyond: The functional puzzles of class C GPCRs. Pharmcol Ther. 2011;130:9–25. doi: 10.1016/j.pharmthera.2011.01.006
5. Vila-Coro AJ, Rodriguez-Frade JM, Martin De Ana A, Moreno-Ortiz MC, Martinez-A C, Mellado M, The chemokine SDF-1α triggers CXCR4 receptor dimerization and activates the JAK/STAT pathway. FASEB J. 1999;13:1699–1710. 10506573
6. Moepps B, Frodl R, Rodewald HR, Baggiolini M, Gierschik P, Two murine homologues of the human chemokine receptor CXCR4 mediating stromal cell-derived factor 1α activation of Gi2 are differentially expressed in vivo. Europ J Immun. 1997;27:2102–2112. doi: 10.1002/eji.18302708399295051
7. Jazin EE, Söderström S, Ebendal T, Larhammar D, Embryonic expression of the mRNA for the rat homologue of the fusin/CXCR-4 HIV-1 co-receptor. J Neuroimmunol. 1997;79:148–154. doi: 10.1016/S0165-5728(97)00117-39394787
8. Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001;410:50–56. doi: 10.1038/3506501611242036
9. Kang H, Watkins G, Douglas-Jones A, Mansel RE, Jiang WG, The elevated level of CXCR4 is correlated with nodal metastasis of human breast cancer. Breast. 2005;14:360–367. doi: 10.1016/j.breast.2004.12.00716216737
10. Feng Y, Broder CC, Kennedy PE, Berger EA, HIV-1 Entry Cofactor: Functional cDNA Cloning of a Seven-Transmembrane, G Protein-Coupled Receptor. Science. 1996;272:872–877. doi: 10.1126/science.272.5263.8728629022
11. Babcock GJ, Farzan M, Sodroski J, Ligand-independent dimerization of CXCR4, a principal HIV-1 coreceptor. J Biol Chem. 2003;278:3378–3385. doi: 10.1074/jbc.M21014020012433920
12. Toth PT, Ren D, Miller RJ, Regulation of CXCR4 receptor dimerization by the chemokine SDF-1α and the HIV-1 coat protein gp120: a fluorescence resonance energy transfer (FRET) study. J Pharmacol Exp Ther. 2004;310:8–17. doi: 10.1124/jpet.103.06495615014135
13. Veldkamp CT, Seibert C, Peterson FC, De la Cruz NB, Haugner JC, Basnet H, et al. Structural basis of CXCR4 sulfotyrosine recognition by the chemokine SDF-1/CXCL12. Sci Signal. 2008;1:ra4. doi: 10.1126/scisignal.116075518799424
14. Nguyen DH, Taub D, CXCR4 function requires membrane cholesterol: implications for HIV infection. J Immunol. 2002;168:4121–4126. doi: 10.4049/jimmunol.168.8.412111937572
15. Wang J, He L, Combs CA, Roderiquez G, Norcross MA, Dimerization of CXCR4 in living malignant cells: control of cell migration by a synthetic peptide that reduces homologous CXCR4 interactions. Mol Cancer Ther. 2006;5:2474–2483. doi: 10.1158/1535-7163.MCT-05-026117041091
16. Percherancier Y, Berchiche YA, Slight I, Volkmer-Engert R, Tamamura H, Fujii N, et al. Bioluminescence resonance energy transfer reveals ligand-induced conformational changes in CXCR4 homo- and heterodimers. J Biol Chem. 2005;280(11):9895–9903. doi: 10.1074/jbc.M41115120015632118
17. Wu B, Chien EY, Mol CD, Fenalti G, Liu W, Katritch V, et al. Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science. 2010;330:1066–1071. doi: 10.1126/science.119439620929726
18. Rosenbaum DM, Rasmussen SGF, Kobilka BK, The structure and function of G-protein-coupled receptors. Nature. 2009;459:356–363. doi: 10.1038/nature0814419458711
19. Katritsch V, Cherezov V, Stevens RC, Diversity and modularity of G protein-coupled receptor structures. Trends Pharmacol Sci. 2012;33:17–27. doi: 10.1016/j.tips.2011.09.003
20. Park JH, Scheerer P, Hofmann KP, Choe HW, Ernst OP, Crystal structure of the ligand-free G-protein-coupled receptor opsin. Nature. 2008;454:183–187. doi: 10.1038/nature0706318563085
21. Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SGF, Thian FS, Kobilka TS, et al. High-Resolution Crystal Structure of an Engineered Human β2-Adrenergic G Protein-Coupled Receptor. Science. 2007;318:1258–1265. doi: 10.1126/science.115057717962520
22. Wu H, Wacker D, Mileni M, Katritch V, Han GW, Vardy E, et al. Structure of the human κ-opioid receptor in complex with JDTic. Nature. 2012;485:327–332. doi: 10.1038/nature1093922437504
23. Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, et al. Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor. Science. 2000;289:739–745. doi: 10.1126/science.289.5480.73910926528
24. Fotiadis D, Liang Y, Filipek S, Saperstein DA, Engel A, Palczewski K, The G protein-coupled receptor rhodopsin in the native membrane. FEBS Letters. 2004;564:281–288. doi: 10.1016/S0014-5793(04)00194-215111110
25. Tan Q, Zhu Y, Li J, Chen Z, Won Han G, Kufareva I, et al. Structure of the CCR5 Chemokine Receptor-HIV Entry Inhibitor Maraviroc Complex. Science. 2013;341:1387–1390. doi: 10.1126/science.124147524030490
26. Huang J, Chen S, Zhang JJ, Huang XY, Crystal Structure of Oligomeric β1-Adrenergic G Protein-Coupled Receptors in Ligand-Free Basal State. Nat Struct Mol Biol. 2013;20:419–425. doi: 10.1038/nsmb.250423435379
27. Qin L, Kufareva I, Holden LG, Wang C, Zheng Y, Zhao C, et al. Structural biology. Crystal structure of the chemokine receptor CXCR4 in complex with a viral chemokine. Science. 2015;347(6226):1117–1122. doi: 10.1126/science.126106425612609
28. Periole X, Huber T, Marrink SJ, Sakmar TP, G Protein-Coupled Receptors Self-Assemble in Dynamics Simulations of Model Bilayers. J Am Chem Soc. 2007;129:10126–10132. doi: 10.1021/ja070624617658882
29. Provasi D, Boz MB, Johnston JM, Filizola M, Preferred Supramolecular Organization and Dimer Interfaces of Opioid Receptors from Simulated Self-Association. PLoS Comput Biol. 2015;11:e1004148. doi: 10.1371/journal.pcbi.100414825822938
30. Wassenaar TA, Pluhackova K, Moussatova A, Sengupta D, Marrink SJ, Tieleman DP, et al. High-Throughput Simulations of Dimer and Trimer Assembly of Membrane Proteins. The DAFT Approach. J Chem Theory Comput. 2015;11:2278–2291. doi: 10.1021/ct501009226574426
31. Prasanna X, Chattopadhyay A, Sengupta D, Cholesterol modulates the dimer interface of the β-adrenergic receptor via cholesterol occupancy sites. Biophys J. 2014;106:1290–1300. doi: 10.1016/j.bpj.2014.02.00224655504
32. Johnston JM, Wang H, Provasi D, Filizola M, Assessing the relative stability of dimer interfaces in G protein-coupled receptors. PLoS Comput Biol. 2012;8:e1002649. doi: 10.1371/journal.pcbi.100264922916005
33. Periole X, Knepp AM, Sakmar TP, Marrink SJ, Huber T, Structural determinants of the supramolecular organization of G protein-coupled receptors in bilayers. J Am Chem Soc. 2012;134:10959–10965. doi: 10.1021/ja303286e22679925
34. Guo W, Shi L, Filizola M, Weinstein H, Javitch JA, Crosstalk in G protein-coupled receptors: Changes at the transmembrane homodimer interface determine activation. Proc Natl Acad Sci USA. 2005;102:17495–17500. doi: 10.1073/pnas.050895010216301531
35. Xue L, Rovira X, Scholler P, Zhao H, Liu J, Pin JP, et al. Major ligand-induced rearrangement of the heptahelical domain interface in a GPCR dimer. Nat Chem Biol. 2015;11:134–140. doi: 10.1038/nchembio.171125503927
36. Mancia F, Assur Z, Herman AG, Siegel R, Hendrickson WA, Ligand sensitivity in dimeric associations of the serotonin 5HT2c receptor. EMBO Reports. 2008;9:363–369. doi: 10.1038/embor.2008.2718344975
37. Liu W, Chun E, Thompson AA, Chubukov P, Xu F, Katritch V, et al. Structural basis for allosteric regulation of GPCRs by sodium ions. Science. 2012;337(6091):232–236. doi: 10.1126/science.121921822798613
38. Zhang K, Zhang J, Gao ZG, Zhang D, Zhu L, Han GW, et al. Structure of the human P2Y12 receptor in complex with an antithrombotic drug. Nature. 2014;509(7498):115–118. doi: 10.1038/nature1308324670650
39. Manglik A, Kruse AC, Kobilka TS, Thian FS, Mathiesen JM, Sunahara RK, et al. Crystal structure of the μ-opioid receptor bound to a morphinan antagonist. Nature. 2012;485:321–326. doi: 10.1038/nature1095422437502
40. Huang W, Manglik A, Venkatakrishnan AJ, Laeremans T, Feinberg EN, Sanborn AL, et al. Structural insights into μ-opioid receptor activation. Nature. 2015;524(7565):315–321. doi: 10.1038/nature1488626245379
41. Liu JJ, Horst R, Katritch V, Stevens RC, Wüthrich K, Biased Signaling Pathways in β2-Adrenergic Receptor Characterized by 19F-NMR. Science. 2012;335:1106–1110. doi: 10.1126/science.121580222267580
42. Botelho AV, Huber T, Sakmar TP, Brown MF, Curvature and hydrophobic forces drive oligomerization and modulate activity of rhodopsin in membranes. Biophys J. 2006;91(12):4464–4477. doi: 10.1529/biophysj.106.08277617012328
43. Hanson MA, Cherezov V, Griffith MT, Roth CB, Jaakola VP, Chien EY, et al. A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor. Structure. 2008;16(6):897–905. doi: 10.1016/j.str.2008.05.00118547522
44. Sengupta D, Chattopadhyay A, Identification of Cholesterol Binding Sites in the Serotonin1A Receptor. J Phys Chem B. 2012;116(43):12991–12996. doi: 10.1021/jp309888u23067252
45. Zhukovsky MA, Lee PH, Ott A, Helms V, Putative cholesterol-binding sites in human immunodeficiency virus (HIV) coreceptors CXCR4 and CCR5. Proteins. 2013;81:555–567. doi: 10.1002/prot.2421123161741
46. Pronk S, Páll S, Schulz R, Larsson P, Bjelkmar P, Apostolov R, et al. GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics. 2013;29:845–854. doi: 10.1093/bioinformatics/btt05523407358
47. De Jong DH, Singh G, Bennett WFD, Arnarez C, Wassenaar TA, Schäfer LV, et al. Improved Parameters for the Martini Coarse-Grained Protorce Field. J Chem Theory Comput. 2013;9:687–697. doi: 10.1021/ct300646g26589065
48. Wassenaar TA, Pluhackova K, Böckmann RA, Marrink SJ, Tieleman DP, Going Backward: A Flexible Geometric Approach to Reverse Transformation from Coarse Grained to Atomistic Models. J Chem Theory Comput. 2014;10:676–690. doi: 10.1021/ct400617g26580045
49. Sali A, Potterton L, Yuan F, van Vlijmen H, M K, Evaluation of comparative protein modeling by MODELLER. Proteins. 1995;23:318–326. doi: 10.1002/prot.3402303068710825
50. Schmid N, Eichenberger AP, Choutko A, Riniker S, Winger M, Mark AE, et al. Definition and testing of the GROMOS force-field versions 54A7 and 54B7. Europ Biophys J. 2011;40(7):843–856. doi: 10.1007/s00249-011-0700-9
51. Marrink SJ, de Vries AH, Mark AE, Coarse Grained Model for Semiquantitative Lipid Simulations. J Phys Chem B. 2004;108:750–760. doi: 10.1021/jp036508g
52. Marrink SJ, Risselada HJ, Yefimov S, Tieleman DP, de Vries AH, The MARTINI Force Field: Coarse Grained Model for Biomolecular Simulations. J Phys Chem B. 2007;111:7812–7824. doi: 10.1021/jp071097f17569554
53. Pluhackova K, Wassenaar TA, Böckmann RA, Rapaport D, Herrmann JM, Molecular Dynamics Simulations of Membrane Proteins. In: Membrane Biogenesis. vol. 1033 of Methods in Molecular Biology. Humana Press; 2013. p. 85–101.
54. Wassenaar TA, Ingólfsson HI, Böckmann RA, Tieleman DP, Marrink SJ, Computational Lipidomics with insane: A Versatile Tool for Generating Custom Membranes for Molecular Simulations. J Chem Theory Comput. 2015;11(5):2144–2155. doi: 10.1021/acs.jctc.5b0020926574417
55. Wassenaar TA, Ingólfsson HI, Prieß M, Marrink SJ, Schäfer LV, Mixing MARTINI: Electrostatic Coupling in Hybrid Atomistic–Coarse-Grained Biomolecular Simulations. J Phys Chem B. 2013;117:3516–3530. doi: 10.1021/jp311533p23406326
56. Berendsen HJC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR, Molecular dynamics with coupling to an external bath. J Chem Phys. 1984;81:3684–3690. doi: 10.1063/1.448118
57. Abraham MJ, Murtola T, Schulz R, Páll S, Smith JC, Hess B, et al. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX. 2015;1–2:19–25. doi: 10.1016/j.softx.2015.06.001
58. Best RB, Zhu X, Shim J, Lopes PEM, Mittal J, Feig M, et al. Optimization of the Additive CHARMM All-Atom Protein Force Field Targeting Improved Sampling of the Backbone Φ, ψ and Side-Chain χ1 and χ2 Dihedral Angles. J Chem Theory Comput. 2012;8(9):3257–3273. doi: 10.1021/ct300400x23341755
59. Klauda JB, Venable RM, Freites JA, O’Connor JW, Tobias DJ, Mondragon-Ramirez C, et al. Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types. J Phys Chem B. 2010;114(23):7830–7843. doi: 10.1021/jp101759q20496934
60. Maier JA, Martinez C, Kasavajhala K, Wickstrom L, Hauser KE, Simmerling C, ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB. J Chem Theory Comput. 2015;11(8):3696–3713. doi: 10.1021/acs.jctc.5b0025526574453
61. Dickson CJ, Madej BD, Skjevik AA, Betz RM, Teigen K, Gould IR, et al. Lipid14: The Amber Lipid Force Field. J Chem Theory Comput. 2014;10(2):865–879. doi: 10.1021/ct401030724803855
62. Åqvist J, Ion-water interaction potentials derived from free energy perturbation simulations. J Phys Chem. 1990;94(21):8021–8024. doi: 10.1021/j100384a009
63. Bussi G, Donadio D, Parrinello M, Canonical sampling through velocity rescaling. J Chem Phys. 2007;126(1):014101. doi: 10.1063/1.240842017212484
64. Darden T, York D, Pedersen L, Particle mesh Ewald: An N ⋅ log(N) method for Ewald sums in large systems. J Chem Phys. 1993;98(12):10089–10092. doi: 10.1063/1.464397
65. Pluhackova K, Kirsch SA, Han J, Sun L, Jiang Z, Unruh T, et al. A critical comparison of biomembrane force fields: structure and dynamics of model DMPC, POPC, and POPE bilayers. J Phys Chem B. 2016;120(16):3888–3903. doi: 10.1021/acs.jpcb.6b0187027035634
66. De Jong DH, Schäfer LV, De Vries AH, Marrink SJ, Berendsen HJC, Grubmüller H, Determining equilibrium constants for dimerization reactions from molecular dynamics simulations. J Comput Chem. 2011;32(9):1919–1928. doi: 10.1002/jcc.2177621469160
67. Vincent L, Soille P, Watersheds in digital spaces: an efficient algorithm based on immersion simulations. IEEE Trans Pattern Anal Mach Intell. 1991;13(6):583–598. doi: 10.1109/34.87344