PtdIns(4,5)P2 stabilizes active states of GPCRs and enhances selectivity of G-protein coupling

Nature

Volumn 559, Issue 7714, 2018, Pages 423-427

  Yen, Hsin Yung ^a,b   Hoi, Kin Kuan ^a   Liko, Idlir ^a,b   Hedger, George ^c   Horrell, Michael R ^c   Song, Wanling ^c   Wu, Di ^a   Heine, Philipp ^d   Warne, Tony ^e   Lee, Yang ^e   Carpenter, Byron ^e,f   Plückthun, Andreas ^d   Tate, Christopher G ^e   Sansom, Mark S P ^c   Robinson, Carol V ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b OMass Technologies Ltd   (United Kingdom)

^c UNIVERSITY OF OXFORD   (United Kingdom)

^d UNIVERSITY OF ZURICH   (Switzerland)

^e MRC LABORATORY OF MOLECULAR BIOLOGY   (United Kingdom)

^f UNIVERSITY OF WARWICK   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE A2A RECEPTOR; BETA 1 ADRENERGIC RECEPTOR; G PROTEIN COUPLED RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; GUANOSINE TRIPHOSPHATE; LIPID; NEUROTENSIN RECEPTOR; PHOSPHATIDYLINOSITOL 4,5 BISPHOSPHATE; ALPHA 2 ADRENERGIC RECEPTOR; HETEROTRIMERIC GUANINE NUCLEOTIDE BINDING PROTEIN; INHIBITORY GUANINE NUCLEOTIDE BINDING PROTEIN; NEUROTENSIN TYPE 1 RECEPTOR; SINGLE CHAIN FRAGMENT VARIABLE ANTIBODY; STIMULATORY GUANINE NUCLEOTIDE BINDING PROTEIN;

ANTIBODY; CHEMICAL BINDING; CHEMICAL COMPOUND; GAS PHASE REACTION; PROTEIN; STABILIZATION; TURNOVER;

ARTICLE; BINDING AFFINITY; BINDING SITE; FORCE; MASS SPECTROMETRY; NONHUMAN; PRIORITY JOURNAL; PROTEIN LIPID INTERACTION; PROTEIN STABILITY; PROTEIN SUBUNIT; TURNOVER TIME; ANIMAL; CHEMISTRY; ENZYME SPECIFICITY; GENETICS; HUMAN; METABOLISM; MOLECULAR DYNAMICS; RAT; TURKEY (BIRD);

ANIMALS; GTP-BINDING PROTEIN ALPHA SUBUNITS, GI-GO; GTP-BINDING PROTEIN ALPHA SUBUNITS, GS; HETEROTRIMERIC GTP-BINDING PROTEINS; HUMANS; MOLECULAR DYNAMICS SIMULATION; PHOSPHATIDYLINOSITOL 4,5-DIPHOSPHATE; PROTEIN STABILITY; RATS; RECEPTORS, ADRENERGIC, ALPHA-2; RECEPTORS, ADRENERGIC, BETA-1; RECEPTORS, G-PROTEIN-COUPLED; RECEPTORS, NEUROTENSIN; SINGLE-CHAIN ANTIBODIES; SUBSTRATE SPECIFICITY; TURKEYS;

EID: 85050176202     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/s41586-018-0325-6     Document Type: Article

References (53)

1. Hauser, A. S., Attwood, M. M., Rask-Andersen, M., Schiöth, H. B. & Gloriam, D. E. Trends in GPCR drug discovery: new agents, targets and indications. Nat. Rev. Drug Discov. 16, 829-842 (2017).
2. Nehmé, R. et al. Mini-G proteins: Novel tools for studying GPCRs in their active conformation. PLoS One 12, e0175642 (2017).
3. Zocher, M., Zhang, C., Rasmussen, S. G., Kobilka, B. K. & Muller, D. J. Cholesterol increases kinetic, energetic, and mechanical stability of the human 2-adrenergic receptor. Proc. Natl Acad. Sci. USA 109, E3463-E3472 (2012).
4. Dawaliby, R. et al. Allosteric regulation of G protein-coupled receptor activity by phospholipids. Nat. Chem. Biol. 12, 35-39 (2016).
5. Gault, J. et al. High-resolution mass spectrometry of small molecules bound to membrane proteins. Nat. Methods 13, 333-336 (2016).
6. Yen, H. Y. et al. Ligand binding to A G protein-coupled receptor captured in A mass spectrometer. Sci. Adv. 3, e1701016 (2017).
7. Egloff, P. et al. Structure of signaling-competent neurotensin receptor 1 obtained by directed evolution in Escherichia coli. Proc. Natl Acad. Sci. USA 111, E655-E662 (2014).
8. Inagaki, S., Ghirlando, R. & Grisshammer, R. Biophysical characterization of membrane proteins in nanodiscs. Methods 59, 287-300 (2013).
9. Hedger, G. & Sansom, M. S. P. Lipid interaction sites on channels, transporters and receptors: Recent insights from molecular dynamics simulations. BBA-Biomembranes 1858, 2390-2400, (2016).
10. Schlinkmann, K. M. et al. Critical features for biosynthesis, stability, and functionality of A G protein-coupled receptor uncovered by all-versus-all mutations. Proc. Natl Acad. Sci. USA 109, 9810-9815 (2012).
11. Carpenter, B., Nehmé, R., Warne, T., Leslie, A. G. W. & Tate, C. G. Structure of the adenosine A2A receptor bound to an engineered G protein. Nature 536, 104-107 (2016).
12. Rasmussen, S. G. et al. Structure of A nanobody-stabilized active state of the 2 adrenoceptor. Nature 469, 175-180 (2011).
13. Hansen, S. B., Tao, X. & MacKinnon, R. Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2. 2. Nature 477, 495-498 (2011).
14. Roux, B. The calculation of the potential of mean force using computer simulations. Comput. Phys. Commun. 91, 275-282 (1995).
15. Domaski, J., Hedger, G., Best, R. B., Stansfeld, P. J. & Sansom, M. S. P. Convergence and sampling in determining free energy landscapes for membrane protein association. J. Phys. Chem. B 121, 3364-3375 (2017).
16. Roth, C. B., Hanson, M. A. & Stevens, R. C. Stabilization of the human 2-adrenergic receptor TM4-TM3-TM5 helix interface by mutagenesis of Glu1223. 41, A critical residue in GPCR structure. J. Mol. Biol. 376, 1305-1319 (2008).
17. Che, T. et al. Structure of the nanobody-stabilized active state of the kappa opioid receptor. Cell 172, 55-67 e15, (2018).
18. Miller-Gallacher, J. L. et al. The 2. 1 Å resolution structure of cyanopindololbound 1-adrenoceptor identifies an intramembrane Na+ ion that stabilises the ligand-free receptor. PLoS One 9, e92727 (2014).
19. Injin, B. & Hee-Jung, C. Structural features of 2 adrenergic receptor: crystal structures and beyond. Mol. Cells 38, 105-111 (2015).
20. Venkatakrishnan, A. J. et al. Diverse activation pathways in class A GPCRs converge near the G-protein-coupling region. Nature 536, 484-487 (2016).
21. Zheng, Y. et al. Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists. Nature 540, 458-461 (2016).
22. Liu, X. et al. Mechanism of intracellular allosteric 2AR antagonist revealed by X-ray crystal structure. Nature 548, 480-484 (2017).
23. Gavi, S., Shumay, E., Wang, H. Y. & Malbon, C. C. G-protein-coupled receptors and tyrosine kinases: crossroads in cell signaling and regulation. Trends Endocrinol. Metab. 17, 48-54 (2006).
24. Scott, D. J., Kummer, L., Egloff, P., Bathgate, R. A. D. & Plückthun, A. Improving the apo-state detergent stability of NTS1 with CHESS for pharmacological and structural studies. BBA-Biomembranes 1838, 2817-2824, (2014).
25. Carpenter, B. & Tate, C. G. Engineering A minimal G protein to facilitate crystallisation of G protein-coupled receptors in their active conformation. Protein Eng. Des. Sel. 29, 583-594 (2016).
26. Warne, T. et al. Structure of A 1-adrenergic G-protein-coupled receptor. Nature 454, 486-491 (2008).
27. Warne, T. et al. The structural basis for agonist and partial agonist action on A 1-adrenergic receptor. Nature 469, 241-244 (2011).
28. Warne, T., Serrano-Vega, M. J., Tate, C. G. & Schertler, G. F. Development and crystallization of A minimal thermostabilised G protein-coupled receptor. Protein Expr. Purif. 65, 204-213 (2009).
29. Warne, T., Chirnside, J. & Schertler, G. F. Expression and purification of truncated, non-glycosylated turkey beta-adrenergic receptors for crystallization. Biochim. Biophys. Acta 1610, 133-140 (2003).
30. Carpenter, B. & Tate, C. G. Expression and Purification of Mini G Proteins from Escherichia coli. Bio Protoc. 7, (2017).
31. Ring, A. M. et al. Adrenaline-activated structure of 2-adrenoceptor stabilized by an engineered nanobody. Nature 502, 575-579 (2013).
32. Hillenbrand, M., Schori, C., Schoppe, J. & Pluckthun, A. Comprehensive analysis of heterotrimeric G-protein complex diversity and their interactions with GPCRs in solution. Proc. Natl Acad. Sci. USA 112, E1181-E1190 (2015).
33. Laganowsky, A., Reading, E., Hopper, J. T. S. & Robinson, C. V. Mass spectrometry of intact membrane protein complexes. Nat. Protocols 8, 639-651 (2013).
34. Chen, P. S., Toribara, T. Y. & Warner, H. Microdetermination of phosphorus. Anal. Chem. 28, 1756-1758 (1956).
35. Marty, M. T. et al. Bayesian deconvolution of mass and ion mobility spectra: from binary interactions to polydisperse ensembles. Anal. Chem. 87, 4370-4376 (2015).
36. Bird, S. S., Marur, V. R., Sniatynski, M. J., Greenberg, H. K. & Kristal, B. S. Lipidomics profiling by high resolution LC-MS and HCD fragmentation: focus on characterization of mitochondrial cardiolipins and monolysocardiolipins. Anal. Chem. 83, 940-949 (2011).
37. Bechara, C. et al. A subset of annular lipids is linked to the flippase activity of an ABC transporter. Nat. Chem. 7, 255-262 (2015).
38. Egloff, P., Deluigi, M., Heine, P., Balada, S. & Pluckthun, A. A cleavable ligand column for the rapid isolation of large quantities of homogeneous and functional neurotensin receptor 1 variants from E. coli. Protein Expr. Purif. 108, 106-114 (2015).
39. Sobott, F., Hernández, H., McCammon, M. G., Tito, M. A. & Robinson, C. V. A tandem mass spectrometer for improved transmission and analysis of large macromolecular assemblies. Anal. Chem. 74, 1402-1407 (2002).
40. Šali, A. & Blundell, T. L. Comparative protein modelling by satisfaction of spatial restraints. J. Mol. Biol. 234, 779-815 (1993).
41. Hess, B., Kutzner, C., van der Spoel, D. & Lindahl, E. GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J. Chem. Theory Comput. 4, 435-447 (2008).
42. de Jong, D. H. et al. Improved parameters for the Martini coarse-grained protein force field. J. Chem. Theory Comput. 9, 687-697 (2013).
43. Koldsø, H., Shorthouse, D., Hélie, J. & Sansom, M. S. P. Lipid clustering correlates with membrane curvature as revealed by molecular simulations of complex lipid bilayers. PLOS Comput. Biol. 10, e1003911 (2014).
44. Periole, X., Cavalli, M., Marrink, S. J. & Ceruso, M. A. Combining an elastic network with A coarse-grained molecular force field: structure, dynamics, and intermolecular recognition. J. Chem. Theory Comput. 5, 2531-2543 (2009).
45. Berendsen, H. J. C., Postma, J. P. M., van Gunsteren, W. F., DiNola, A. & Haak, J. R. Molecular dynamics with coupling to an external bath. J. Chem. Phys. 81, 3684-3690 (1984).
46. Tironi, I. G., Sperb, R., Smith, P. E. & van Gunsteren, W. F. A generalized reaction field method for molecular dynamics simulations. J. Chem. Phys. 102, 5451-5459 (1995).
47. Hess, B., Bekker, H., Berendsen, H. J. C. & Fraaije, J. G. E. M. LINCS: A linear constraint solver for molecular simulations. J. Comput. Chem. 18, 1463-1472 (1997).
48. Humphrey, W., Dalke, A. & Schulten, K. VMD: visual molecular dynamics. J. Mol. Graph. 14, 33-38 (1996).
49. Hedger, G., Sansom, M. S. P. & Koldsø, H. The juxtamembrane regions of human receptor tyrosine kinases exhibit conserved interaction sites with anionic lipids. Sci. Rep. 5, 9198 (2015).
50. Hedger, G., Shorthouse, D., Koldso, H. & Sansom, M. S. Free energy landscape of lipid interactions with regulatory binding sites on the transmembrane domain of the EGF receptor. J. Phys. Chem. B 120, 8154-8163 (2016).
51. Hub, J. S., de Groot, B. L. & van der Spoel, D. g-wham-A free weighted histogram analysis implementation including robust error and autocorrelation estimates. J. Chem. Theory Comput. 6, 3713-3720 (2010).
52. Notredame, C., Higgins, D. G. & Heringa, J. T-coffee: A novel method for fast and accurate multiple sequence alignment. J. Mol. Biol. 302, 205-217 (2000).
53. Bond, C. S. & Schuttelkopf, A. W. ALINE: A WYSIWYG protein-sequence alignment editor for publication-quality alignments. Acta Crystallogr. D 65, 510-512 (2009).