An analysis of oligomerization interfaces in transmembrane proteins

BMC Structural Biology

Guido Capitani¹  Kumaran Baskaran¹  Nikhil Biyani¹  Jose M Duarte¹ 

[1] Laboratory of Biomolecular Research, Paul Scherrer Institut, Villigen, 5232, Switzerland

关键词: GPCR;    Lipids;    Eppic;    Membrane proteins;    Protein-protein interfaces;    Protein structure;   

Others  :  793859
DOI  :  10.1186/1472-6807-13-21

 received in 2013-06-21, accepted in 2013-10-11,  发布年份 2013

【 摘 要 】

Background

The amount of transmembrane protein (TM) structures solved to date is now large enough to attempt large scale analyses. In particular, extensive studies of oligomeric interfaces in the transmembrane region are now possible.

Results

We have compiled the first fully comprehensive set of validated transmembrane protein interfaces in order to study their features and assess what differentiates them from their soluble counterparts.

Conclusions

The general features of TM interfaces do not differ much from those of soluble proteins: they are large, tightly packed and possess many interface core residues. In our set, membrane lipids were not found to significantly mediate protein-protein interfaces. Although no G protein-coupled receptor (GPCR) was included in the validated set, we analyzed the crystallographic dimerization interfaces proposed in the literature. We found that the putative dimer interfaces proposed for class A GPCRs do not show the usual patterns of stable biological interfaces, neither in terms of evolution nor of packing, thus they likely correspond to crystal interfaces. We cannot however rule out the possibility that they constitute transient or weak interfaces. In contrast we do observe a clear signature of biological interface for the proposed dimer of the class F human Smoothened receptor.

【 授权许可】

   
2013 Duarte et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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【 参考文献 】

• [1]Deisenhofer J, Epp O, Miki K, Huber R, Michel H: Structure of the protein subunits in the photosynthetic reaction centre of Rhodopseudomonas viridis at 3 Å resolution. Nature 1985, 318:618-624.
• [2]Ulmschneider MB, Sansom MS: Amino acid distributions in integral membrane protein structures. Biochim Biophys Acta 2001, 1512:1-14.
• [3]Adamian L, Naveed H, Liang J: Lipid-binding surfaces of membrane proteins: evidence from evolutionary and structural analysis. Biochim Biophys Acta 1808, 2011:1092-1102.
• [4]Adamian L, Liang J: Helix-helix packing and interfacial pairwise interactions of residues in membrane proteins. J Mol Biol 2001, 311:891-907.
• [5]Jackups R, Liang J: Interstrand pairing patterns in beta-barrel membrane proteins: the positive-outside rule, aromatic rescue, and strand registration prediction. J Mol Biol 2005, 354:979-993.
• [6]Duarte JM, Srebniak A, Schärer MA, Capitani G: Protein interface classification by evolutionary analysis. BMC Bioinformatics 2012, 13:334.
• [7]Palsdottir H, Hunte C: Lipids in membrane protein structures. Biochim Biophys Acta 2004, 1666:2-18.
• [8]Barrera NP, Zhou M, Robinson CV: The role of lipids in defining membrane protein interactions: insights from mass spectrometry. Trends Cell Biol 2013, 23:1-8.
• [9]Ernst AM, Contreras FX, Brügger B, Wieland F: Determinants of specificity at the protein-lipid interface in membranes. Febs Lett 2010, 584:1713-1720.
• [10]De Meyer FJ-M, Venturoli M, Smit B: Molecular simulations of lipid-mediated protein-protein interactions. Biophys J 2008, 95:1851-1865.
• [11]Periasamy A: Fluorescence resonance energy transfer microscopy: a mini review. J Biomed Opt 2001, 6:287-291.
• [12]Gautier I, Tramier M, Durieux C, Coppey J, Pansu RB, Nicolas JC, Kemnitz K, Coppey-Moisan M: Homo-FRET microscopy in living cells to measure monomer-dimer transition of GFP-tagged proteins. Biophys J 2001, 80:3000-3008.
• [13]Langosch D, Brosig B, Kolmar H, Fritz HJ: Dimerisation of the glycophorin A transmembrane segment in membranes probed with the ToxR transcription activator. J Mol Biol 1996, 263:525-530.
• [14]Russ W, Engelman D: TOXCAT: a measure of transmembrane helix association in a biological membrane. Proc Natl Acad Sci USA 1999, 96:863-868.
• [15]Berger BW, Kulp DW, Span LM, DeGrado JL, Billings PC, Senes A, Bennett JS, DeGrado WF: Consensus motif for integrin transmembrane helix association. Proc Natl Acad Sci USA 2010, 107:703-708.
• [16]Haupts U, Tittor J, Oesterhelt D: Closing in on bacteriorhodopsin: progress in understanding the molecule. Annu Rev Bioph Biom 1999, 28:367-399.
• [17]Essen L-O, Siegert R, Lehmann WD, Oesterhelt D: Lipid patches in membrane protein oligomers: crystal structure of the bacteriorhodopsin-lipid complex. Proc Natl Acad Sci 1998, 95:11673-11678.
• [18]Luecke H, Schobert B, Richter HT, Cartailler JP, Lanyi JK: Structure of bacteriorhodopsin at 1.55 A resolution. J Mol Biol 1999, 291:899-911.
• [19]Brouillette CG, McMichens RB, Stern LJ, Khorana HG: Structure and thermal stability of monomeric bacteriorhodopsin in mixed phospholipid/detergent micelles. Proteins 1989, 5:38-46.
• [20]Grzesiek S, Dencher NA: Monomeric and aggregated bacteriorhodopsin: single-turnover proton transport stoichiometry and photochemistry. Proc Natl Acad Sci USA 1988, 85:9509-9513.
• [21]Faham S, Bowie JU: Bicelle crystallization: a new method for crystallizing membrane proteins yields a monomeric bacteriorhodopsin structure. J Mol Biol 2002, 316:1-6.
• [22]Gurevich VV, Gurevich EV: How and why do GPCRs dimerize? Trends Pharmacol Sci 2008, 29:234-240.
• [23]Chabre M, Le Maire M: Monomeric G-protein-coupled receptor as a functional unit. Biochemistry 2005, 44:9395-9403.
• [24]Park PS-H, Filipek S, Wells JW, Palczewski K: Oligomerization of G protein-coupled receptors: past, present, and future. Biochemistry 2004, 43:15643-15656.
• [25]Wu H, Wacker D, Mileni M, Katritch V, Han GW, Vardy E, Liu W, Thompson AA, Huang X-P, Carroll FI, Mascarella SW, Westkaemper RB, Mosier PD, Roth BL, Cherezov V, Stevens RC: Structure of the human κ-opioid receptor in complex with JDTic. Nature 2012, 485:327-332.
• [26]Salom D, Lodowski DT, Stenkamp RE, Le Trong I, Golczak M, Jastrzebska B, Harris T, Ballesteros JA, Palczewski K: Crystal structure of a photoactivated deprotonated intermediate of rhodopsin. Proc Natl Acad Sci USA 2006, 103:16123-16128.
• [27]Wu B, Chien EYT, Mol CD, Fenalti G, Liu W, Katritch V, Abagyan R, Brooun A, Wells P, Bi FC, Hamel DJ, Kuhn P, Handel TM, Cherezov V, Stevens RC: Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 2010, 330:1066-1071.
• [28]Huang J, Chen S, Zhang JJ, Huang X-Y: Crystal structure of oligomeric β(1)-adrenergic G protein-coupled receptors in ligand-free basal state. Nat Struct Mol Biol 2013, 20:419-425.
• [29]Bamber L, Harding M, Monné M, Slotboom D-J, Kunji ERS: The yeast mitochondrial ADP/ATP carrier functions as a monomer in mitochondrial membranes. Proc Natl Acad Sci U S A 2007, 104:10830-10834.
• [30]Bamber L, Harding M, Butler PJG, Kunji ERS: Yeast mitochondrial ADP/ATP carriers are monomeric in detergents. Proc Natl Acad Sci USA 2006, 103:16224-16229.
• [31]Nury H, Dahout-Gonzalez C, Trézéguet V, Lauquin G, Brandolin G, Pebay-Peyroula E: Structural basis for lipid-mediated interactions between mitochondrial ADP/ATP carrier monomers. Febs Lett 2005, 579:6031-6036.
• [32]Schärer MA, Grütter MG, Capitani G: CRK: an evolutionary approach for distinguishing biologically relevant interfaces from crystal contacts. Proteins 2010, 78:2707-2713.
• [33]Ponstingl H, Kabir T, Thornton JM: Automatic inference of protein quaternary structure from crystals. J Appl Crystallogr 2003, 36:1116-1122.
• [34]Bahadur RP, Chakrabarti P, Rodier F, Janin J: Dissecting subunit interfaces in homodimeric proteins. Proteins 2003, 53:708-719.
• [35]Lawrence MC, Colman PM: Shape complementarity at protein/protein interfaces. J Mol Biol 1993, 234:946-950.
• [36]Eilers M, Shekar SC, Shieh T, Smith SO, Fleming PJ: Internal packing of helical membrane proteins. Proc Natl Acad Sci USA 2000, 97:5796-5801.
• [37]Eilers M, Patel AB, Liu W, Smith SO: Comparison of helix interactions in membrane and soluble alpha-bundle proteins. Biophys J 2002, 82:2720-2736.
• [38]Senes A, Ubarretxena-Belandia I, Engelman DM: The Calpha –-H…O hydrogen bond: a determinant of stability and specificity in transmembrane helix interactions. Proc Natl Acad Sci USA 2001, 98:9056-9061.
• [39]Marsh D: Stoichiometry of lipid-protein interaction and integral membrane protein structure. Eur Biophys J 1997, 26:203-208.
• [40]Huang L-S, Cobessi D, Tung EY, Berry EA: Binding of the respiratory chain inhibitor antimycin to the mitochondrial bc1 complex: a new crystal structure reveals an altered intramolecular hydrogen-bonding pattern. J Mol Biol 2005, 351:573-597.
• [41]Hackenberg H, Klingenberg M: Molecular weight and hydrodynamic parameters of the adenosine 5’-diphosphate–adenosine 5’-triphosphate carrier in Triton X-100. Biochemistry 1980, 19:548-555.
• [42]Pebay-Peyroula E, Dahout-Gonzalez C, Kahn R, Trézéguet V, Lauquin GJ-M, Brandolin G: Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside. Nature 2003, 426:39-44.
• [43]Schobert B, Cupp-Vickery J, Hornak V, Smith S, Lanyi J: Crystallographic structure of the K intermediate of bacteriorhodopsin: conservation of free energy after photoisomerization of the retinal. J Mol Biol 2002, 321:715-726.
• [44]Pozharski E, Weichenberger CX, Rupp B: Techniques, tools and best practices for ligand electron-density analysis and results from their application to deposited crystal structures. Acta Crystallogr D 2013, 69:150-167.
• [45]Li D, Lee J, Caffrey M: Crystallizing membrane proteins in lipidic mesophases. A host lipid screen. Cryst Growth Des 2011, 11:530-537.
• [46]Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SGF, Thian FS, Kobilka TS, Choi H-J, Kuhn P, Weis WI, Kobilka BK, Stevens RC: High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science (New York, N.Y.) 2007, 318:1258-1265.
• [47]Gurevich VV, Gurevich EV: GPCR monomers and oligomers: it takes all kinds. Trends Neurosci 2008, 31:74-81.
• [48]Chun L, Zhang W, Liu J: Structure and ligand recognition of class C GPCRs. Acta Pharm Sinic 2012, 33:312-323.
• [49]Babcock GJ, Farzan M, Sodroski J: Ligand-independent dimerization of CXCR4, a principal HIV-1 coreceptor. J Biol Chem 2003, 278:3378-3385.
• [50]Percherancier Y, Berchiche YA, Slight I, Volkmer-Engert R, Tamamura H, Fujii N, Bouvier M, Heveker N: Bioluminescence resonance energy transfer reveals ligand-induced conformational changes in CXCR4 homo- and heterodimers. J Biol Chem 2005, 280:9895-9903.
• [51]Janin J, Rodier F: Protein-protein interaction at crystal contacts. Proteins 1995, 23:580-587.
• [52]Henrick K, Thornton JM: PQS: a protein quaternary structure file server. Trends Biochem Sci 1998, 23:358-361.
• [53]Valdar WS, Thornton JM: Conservation helps to identify biologically relevant crystal contacts. J Mol Biol 2001, 313:399-416.
• [54]Krissinel E, Henrick K: Inference of macromolecular assemblies from crystalline state. J Mol Biol 2007, 372:774-797.
• [55]Wang C, Wu H, Katritch V, Han GW, Huang X-P, Liu W, Siu FY, Roth BL, Cherezov V, Stevens RC: Structure of the human smoothened receptor bound to an antitumour agent. Nature 2013, 497:338-343.
• [56]Zhao Y, Tong C, Jiang J: Hedgehog regulates smoothened activity by inducing a conformational switch. Nature 2007, 450:252-258.
• [57]Rasmussen SGF, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, Thian FS, Chae PS, Pardon E, Calinski D, Mathiesen JM, Shah STA, Lyons JA, Caffrey M, Gellman SH, Steyaert J, Skiniotis G, Weis WI, Sunahara RK, Kobilka BK: Crystal structure of the β2 adrenergic receptor-Gs protein complex. Nature 2011, 477:549-555.
• [58]Lomize MA, Lomize AL, Pogozheva ID, Mosberg HI: OPM: orientations of proteins in membranes database. Bioinformatics 2006, 22:623-625.
• [59]Tusnády GE, Dosztányi Z, Simon I: Transmembrane proteins in the protein data bank: identification and classification. Bioinformatics 2004, 20:2964-2972.
• [60]Efron B: Bootstrap methods: another look at the jackknife. The annals of Statistics 1979, 7:1-26.
• [61]R Development Core Team: R: A Language and Environment for Statistical Computing. Vienna Austria: R Foundation for Statistical Computing; 2010.
• [62]Kleywegt GJ, Harris MR, Zou JY, Taylor TC, Wählby A, Jones TA: The uppsala electron-density server. Acta Crystallogr D 2004, 60:2240-2249.