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PLOS ONE  2012 

Comparative Analysis of the Heptahelical Transmembrane Bundles of G Protein-Coupled Receptors

DOI: 10.1371/journal.pone.0035802

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Abstract:

Background G protein-coupled receptors represent a large family of eukaryotic membrane proteins, and are involved in almost all physiological processes in humans. Recent advances in the crystallographic study of these receptors enable a detailed comparative analysis of the commonly shared heptahelical transmembrane bundle. Systematic comparison of the bundles from a variety of receptors is indispensable for understanding not only of the structural diversification optimized for the binding of respective ligands but also of the structural conservation required for the common mechanism of activation accompanying the interaction changes among the seven helices. Methodology/Principal Findings We have examined the bundles of 94 polypeptide chains from almost all available structures of 11 receptors, which we classified into either inactivated chain or activated chain, based on the type of bound ligand. For the inactivated chains, superposition of 200 residue bundles by secondary structure matching demonstrated that the bound ligands share a laterally limited cavity in the extracellular section of the bundle. Furthermore, a distinct feature was found for helix III of bovine rhodopsin, which might have evolved to lower its activity in the presence of 11-cis-retinal, to a level that other receptors could hardly achieve with any currently available ligands. Conclusions/Significance Systematic analysis described here would be valuable for understanding of the rearrangement of seven helices which depends on the ligand specificity and activation state of the receptors.

References

[1]  Lefkowitz RJ (2007) Seven transmembrane receptors: something old, something new. Acta Physiol 190: 9–19.
[2]  Krishnan A, Almén MS, Fredriksson R, Schi?th HB (2012) The origin of GPCRs: identification of mammalian like Rhodopsin, Adhesion, Glutamate and Frizzled GPCRs in fungi. PLoS One 7: e29817.
[3]  Haga K, Kruse AC, Asada H, Yurugi-Kobayashi T, Shiroishi M, et al. (2012) Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist. Nature 482: 547–551.
[4]  Kruse AC, Hu J, Pan AC, Arlow DH, Rosenbaum DM, et al. (2012) Structure and dynamics of the M3 muscarinic acetylcholine receptor. Nature 482: 552–556.
[5]  Hanson MA, Roth CB, Jo E, Griffith MT, Scott FL, et al. (2012) Crystal structure of a lipid G protein–coupled receptor. Science 335: 851–855.
[6]  Congreve M, Langmead CJ, Mason JS, Marshall FH (2011) Progress in structure based drug design for G protein-coupled receptors. J Med Chem 54: 4283–4311.
[7]  Katritch V, Cherezov V, Stevens RC (2012) Diversity and modularity of G protein-coupled receptor structures. Trends Pharmacol Sci 33: 17–27.
[8]  Xu F, Wu H, Katritch V, Han GW, Jacobson KA, et al. (2011) Structure of an agonist-bound human A2A adenosine receptor. Science 332: 322–327.
[9]  Warne T, Moukhametzianov R, Baker JG, Nehmé R, Edwards PC, et al. (2011) The structural basis for agonist and partial agonist action on a β(1)-adrenergic receptor. Nature 469: 241–244.
[10]  Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, et al. (2000) Crystal structure of rhodopsin: a G protein-coupled receptor. Science 289: 739–745.
[11]  Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, et al. (2007) High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 318: 1258–1265.
[12]  Krissinel E, Henrick K (2004) Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions. Acta Crystallogr D60: 2256–2268.
[13]  Emsley P, Lohkamp B, Scott WG, Cowtan K (2010) Features and development of Coot. Acta Crystallogr D66: 486–501.
[14]  Winn MD, Ballard CC, Cowtan KD, Dodson EJ, Emsley P, et al. (2011) Overview of the CCP4 suite and current developments. Acta Crystallogr D67: 235–242.
[15]  Ballesteros JA, Weinstein H (1995) Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors. Methods Neurosci 25: 366–428.
[16]  Warne T, Serrano-Vega MJ, Baker JG, Moukhametzianov R, Edwards PC, et al. (2008) Structure of a β1-adrenergic G-protein-coupled receptor. Nature 454: 486–491.
[17]  Moukhametzianov R, Warne T, Edwards PC, Serrano-Vega MJ, Leslie AG, et al. (2011) Two distinct conformations of helix 6 observed in antagonist-bound structures of a β1-adrenergic receptor. Proc Natl Acad Sci USA 108: 8228–8232.
[18]  Okada T, Palczewski K (2001) Crystal structure of rhodopsin: implications for vision and beyond. Curr Opin Struct Biol 11: 420–426.
[19]  Schertler GF, Villa C, Henderson R (1993) Projection structure of rhodopsin. Nature 362: 770–772.
[20]  Kabsch W, Sander C (1983) Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22: 2577–2637.
[21]  Robinson PR, Cohen GB, Zhukovsky EA, Oprian DD (1992) Constitutively active mutants of rhodopsin. Neuron 9: 719–725.
[22]  Nakamichi H, Okada T (2006) Crystallographic analysis of primary visual photochemistry. Angew Chem Int Ed 45: 4270–4273.
[23]  Nakamichi H, Okada T (2006) Proc Natl Acad Sci USA 103: 12729–12734.
[24]  Farrens DL, Altenbach C, Yang K, Hubbell WL, Khorana HG (1996) Requirement of rigid-body motion of transmembrane helices for light activation of rhodopsin. Science 274: 768–770.
[25]  Park JH, Scheerer P, Hofmann KP, Choe HW, Ernst OP (2008) Crystal structure of the ligand-free G-protein-coupled receptor opsin. Nature 454: 183–187.
[26]  Rasmussen SG, DeVree BT, Zou Y, Kruse AC, Chung KY, et al. (2011) Crystal structure of the β2 adrenergic receptor-Gs protein complex. Nature 477: 549–555.
[27]  Rasmussen SG, Choi HJ, Fung JJ, Pardon E, Casarosa P, et al. (2011) Structure of a nanobody-stabilized active state of the β(2) adrenoceptor. Nature 469: 175–180.
[28]  Han M, Smith SO, Sakmar TP (1998) Constitutive activation of opsin by mutation of methionine 257 on transmembrane helix 6. Biochemistry 37: 8253–8261.
[29]  Lu ZL, Hulme EC (1999) The functional topography of transmembrane domain 3 of the M1 muscarinic acetylcholine receptor, revealed by scanning mutagenesis. J Biol Chem 274: 7309–7315.
[30]  Standfuss J, Edwards PC, D'Antona A, Fransen M, Xie G, et al. (2011) The structural basis of agonist-induced activation in constitutively active rhodopsin. Nature 471: 656–660.
[31]  Okada T, Fujiyoshi Y, Silow M, Navarro J, Landau EM, et al. (2002) Functional role of internal water molecules in rhodopsin revealed by X-ray crystallography. Proc Natl Acad Sci USA 99: 5982–5987.
[32]  Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, et al. (2004) UCSF Chimera–a visualization system for exploratory research and analysis. J Comput Chem 25: 1605–1612.
[33]  McNicholas S, Potterton E, Wilson KS, Noble MEM (2011) Presenting your structures: the CCP4mg molecular-graphics software. Acta Cryst D67: 386–394.

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