Discovery of new GPCR biology: one receptor structure at a time.

G-protein-coupled receptors (GPCRs) are the largest family of proteins in the human genome. Within the last year, we have witnessed a relative explosion in the amount of structural information available for the GPCR family with two new structures of opsin in the presence and absence of transducin peptide, four new structures of beta-adrenergic receptors, and a recent structure of the human adenosine A2A receptor. The new biological insight being gained, such as the highly divergent extracellular loops and areas of structural convergence within the transmembrane helices, allows us to chart a course for further investigation into this important class of membrane proteins.

[1]  Peter Nollert,et al.  Crystallization of membrane proteins in cubo. , 2002, Methods in enzymology.

[2]  V. Cherezov,et al.  Room to move: crystallizing membrane proteins in swollen lipidic mesophases. , 2006, Journal of molecular biology.

[3]  Manfred Burghammer,et al.  Structure of bovine rhodopsin in a trigonal crystal form. , 2003, Journal of molecular biology.

[4]  G. Privé,et al.  Engineering the lac permease for purification and crystallization , 1996, Journal of bioenergetics and biomembranes.

[5]  Gebhard F. X. Schertler,et al.  Structure of a β1-adrenergic G-protein-coupled receptor , 2008, Nature.

[6]  M. L. Ujwal,et al.  The lactose permease meets Frankenstein. , 1994, The Journal of experimental biology.

[7]  R. Stevens,et al.  High-Resolution Crystal Structure of an Engineered Human β2-Adrenergic G Protein–Coupled Receptor , 2007, Science.

[8]  R. Stevens,et al.  GPCR Engineering Yields High-Resolution Structural Insights into β2-Adrenergic Receptor Function , 2007, Science.

[9]  Adam Godzik,et al.  Flexible structure alignment by chaining aligned fragment pairs allowing twists , 2003, ECCB.

[10]  P. Sieving,et al.  Disruption of conserved rhodopsin disulfide bond by Cys187Tyr mutation causes early and severe autosomal dominant retinitis pigmentosa. , 1995, Ophthalmology.

[11]  G J Kleywegt,et al.  Where freedom is given, liberties are taken. , 1995, Structure.

[12]  Oliver P. Ernst,et al.  Crystal structure of opsin in its G-protein-interacting conformation , 2008, Nature.

[13]  H. Schiöth,et al.  The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. , 2003, Molecular pharmacology.

[14]  Vadim Cherezov,et al.  A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor. , 2008, Structure.

[15]  M. Burghammer,et al.  Crystal structure of the human β2 adrenergic G-protein-coupled receptor , 2007, Nature.

[16]  D. Eisenberg,et al.  Fusion proteins as tools for crystallization: the lactose permease from Escherichia coli. , 1994, Acta crystallographica. Section D, Biological crystallography.

[17]  E. Landau,et al.  Structural and mechanistic insight from high resolution structures of archaeal rhodopsins , 2003, FEBS letters.

[18]  Patrick Scheerer,et al.  Crystal structure of the ligand-free G-protein-coupled receptor opsin , 2008, Nature.

[19]  Marcus Elstner,et al.  The retinal conformation and its environment in rhodopsin in light of a new 2.2 A crystal structure. , 2004, Journal of molecular biology.

[20]  L. Birnbaumer,et al.  Studies on the intrinsic activity (efficacy) of human adrenergic receptors. Co-expression of beta 1 and beta 2 reveals a lower efficacy for the beta 1 receptor. , 1994, Texas Heart Institute journal.

[21]  Krzysztof Palczewski,et al.  Crystal structure of a photoactivated deprotonated intermediate of rhodopsin , 2006, Proceedings of the National Academy of Sciences.

[22]  Martin Caffrey,et al.  Membrane protein crystallization. , 2003, Journal of structural biology.

[23]  Tsutomu Kouyama,et al.  Crystal structure of squid rhodopsin , 2008, Nature.

[24]  R. Stevens,et al.  Stabilization of the human beta2-adrenergic receptor TM4-TM3-TM5 helix interface by mutagenesis of Glu122(3.41), a critical residue in GPCR structure. , 2008, Journal of molecular biology.

[25]  M. Caffrey,et al.  A lipid's eye view of membrane protein crystallization in mesophases. , 2000, Current opinion in structural biology.

[26]  Manfred Burghammer,et al.  Crystal structure of a thermally stable rhodopsin mutant. , 2007, Journal of molecular biology.

[27]  Yoko Shibata,et al.  Conformational thermostabilization of the β1-adrenergic receptor in a detergent-resistant form , 2008, Proceedings of the National Academy of Sciences.

[28]  R. Stevens,et al.  The 2.6 Angstrom Crystal Structure of a Human A2A Adenosine Receptor Bound to an Antagonist , 2008, Science.

[29]  K. Palczewski,et al.  Crystal Structure of Rhodopsin: A G‐Protein‐Coupled Receptor , 2002, Chembiochem : a European journal of chemical biology.

[30]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[31]  Tetsuya Hori,et al.  Crystal Structure of Squid Rhodopsin with Intracellularly Extended Cytoplasmic Region , 2008, Journal of Biological Chemistry.

[32]  W. Delano The PyMOL Molecular Graphics System , 2002 .

[33]  Thomas Huber,et al.  Functional role of the "ionic lock"--an interhelical hydrogen-bond network in family A heptahelical receptors. , 2008, Journal of molecular biology.

[34]  Andrei L. Lomize,et al.  OPM: Orientations of Proteins in Membranes database , 2006, Bioinform..

[35]  J. Rosenbusch,et al.  Lipidic cubic phases: a novel concept for the crystallization of membrane proteins. , 1996, Proceedings of the National Academy of Sciences of the United States of America.