Journal ArticleDOI
Molecular signatures of G-protein-coupled receptors.
AJ Venkatakrishnan,Xavier Deupi,Guillaume Lebon,Christopher G. Tate,Gebhard F. X. Schertler,Gebhard F. X. Schertler,M. Madan Babu +6 more
TLDR
Through a systematic analysis of high-resolution GPCR structures, a conserved network of non-covalent contacts that defines the G PCR fold is uncovered and characteristic features of ligand binding and conformational changes during receptor activation are revealed.Abstract:
G-protein-coupled receptors (GPCRs) are physiologically important membrane proteins that sense signalling molecules such as hormones and neurotransmitters, and are the targets of several prescribed drugs. Recent exciting developments are providing unprecedented insights into the structure and function of several medically important GPCRs. Here, through a systematic analysis of high-resolution GPCR structures, we uncover a conserved network of non-covalent contacts that defines the GPCR fold. Furthermore, our comparative analysis reveals characteristic features of ligand binding and conformational changes during receptor activation. A holistic understanding that integrates molecular and systems biology of GPCRs holds promise for new therapeutics and personalized medicine.read more
Citations
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Journal ArticleDOI
Classification of intrinsically disordered regions and proteins.
Robin van der Lee,Robin van der Lee,Marija Buljan,Benjamin Lang,Robert J. Weatheritt,Gary W. Daughdrill,A. Keith Dunker,Monika Fuxreiter,Julian Gough,Joerg Gsponer,David T. Jones,Philip M. Kim,Richard W. Kriwacki,Christopher J. Oldfield,Rohit V. Pappu,Peter Tompa,Peter Tompa,Vladimir N. Uversky,Vladimir N. Uversky,Peter E. Wright,M. Madan Babu +20 more
TL;DR: Characterization of unannotated and uncharacterized protein segments is expected to lead to the discovery of novel functions as well as provide important insights into existing biological processes and is likely to shed new light on molecular mechanisms of diseases that are not yet fully understood.
Journal ArticleDOI
GPCRDB: an information system for G protein-coupled receptors.
TL;DR: New features in the fifth major GPCRdb release are highlighted, including G PCR crystal structure browsing, superposition and display of ligand interactions, direct deposition by users of point mutations and their effects on ligand binding.
Classification of Intrinsically Disordered Regions and Proteins
Robin van der Lee,Robin van der Lee,Marija Buljan,Benjamin Lang,Robert J. Weatheritt,Gary W. Daughdrill,A. Keith Dunker,Monika Fuxreiter,Julian Gough,Joerg Gsponer,David T. Jones,Philip M. Kim,Richard W. Kriwacki,Christopher J. Oldfield,Rohit V. Pappu,Peter Tompa,Peter Tompa,Vladimir N. Uversky,Vladimir N. Uversky,Peter E. Wright,M. Madan Babu +20 more
TL;DR: Uncharacterized and uncharacterized protein segments are likely to be a large source of functional novelty relevant for discovering new biology as discussed by the authors, which is likely to lead to the discovery of novel functions as well as provide important insights into existing biological processes.
Journal ArticleDOI
Microbial and animal rhodopsins: structures, functions, and molecular mechanisms.
Oliver P. Ernst,David T. Lodowski,Marcus Elstner,Peter Hegemann,Leonid S. Brown,Hideki Kandori +5 more
TL;DR: Rhodopsins found in Eukaryotes, Bacteria, and Archaea consist of opsin apoproteins and a covalently linked retinal which is employed to absorb photons for energy conversion or the initiation of intra- or intercellular signaling.
Journal ArticleDOI
The Molecular Basis of G Protein-Coupled Receptor Activation.
William I. Weis,Brian K. Kobilka +1 more
TL;DR: Molecular understanding of the allosteric coupling between ligand binding and G protein or arrestin interaction is emerging from structures of several GPCRs crystallized in inactive and active states, spectroscopic data, and computer simulations.
References
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Journal ArticleDOI
Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor
Krzysztof Palczewski,Takashi Kumasaka,Tetsuya Hori,Craig A. Behnke,H. Motoshima,Brian A. Fox,I. Le Trong,David C. Teller,Tetsuji Okada,Ronald E. Stenkamp,Masaki Yamamoto,Masashi Miyano +11 more
TL;DR: This article determined the structure of rhodopsin from diffraction data extending to 2.8 angstroms resolution and found that the highly organized structure in the extracellular region, including a conserved disulfide bridge, forms a basis for the arrangement of the sevenhelix transmembrane motif.
Journal ArticleDOI
High-Resolution Crystal Structure of an Engineered Human β2-Adrenergic G Protein–Coupled Receptor
Vadim Cherezov,Daniel M. Rosenbaum,Michael A. Hanson,Søren G. F. Rasmussen,Foon Sun Thian,Tong Sun Kobilka,Hee Jung Choi,Peter Kuhn,William I. Weis,Brian K. Kobilka,Raymond C. Stevens +10 more
TL;DR: Although the location of carazolol in the β2-adrenergic receptor is very similar to that of retinal in rhodopsin, structural differences in the ligand-binding site and other regions highlight the challenges in using rhodopin as a template model for this large receptor family.
Journal ArticleDOI
The G-Protein-Coupled Receptors in the Human Genome Form Five Main Families : Phylogenetic Analysis, Paralogon Groups, and Fingerprints
TL;DR: This study represents the first overall map of the GPCR sequences in a single mammalian genome and shows several common structural features indicating that the human GPCRs in the GRAFS families share a common ancestor.
Journal ArticleDOI
Crystal structure of the β2 adrenergic receptor-Gs protein complex.
Søren G. F. Rasmussen,Brian T. DeVree,Yaozhong Zou,Andrew C. Kruse,Ka Young Chung,Tong Sun Kobilka,Foon Sun Thian,Pil Seok Chae,Els Pardon,Els Pardon,Diane M. Calinski,Jesper Mosolff Mathiesen,Syed T. A. Shah,Joseph A. Lyons,Martin Caffrey,Samuel H. Gellman,Jan Steyaert,Jan Steyaert,Georgios Skiniotis,William I. Weis,Roger K. Sunahara,Brian K. Kobilka +21 more
TL;DR: This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR and the most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain.
Book ChapterDOI
[19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors
TL;DR: This chapter discusses the integrated methods for the construction of three-dimensional models and computational probing of structure–function relations in G protein-coupled receptors (GPCR) and expects increased rate of success achieved by molecular modeling and computational simulation methods in providing structural insights relevant to the functions of biological molecules.
Related Papers (5)
Crystal structure of the β2 adrenergic receptor-Gs protein complex.
Søren G. F. Rasmussen,Brian T. DeVree,Yaozhong Zou,Andrew C. Kruse,Ka Young Chung,Tong Sun Kobilka,Foon Sun Thian,Pil Seok Chae,Els Pardon,Els Pardon,Diane M. Calinski,Jesper Mosolff Mathiesen,Syed T. A. Shah,Joseph A. Lyons,Martin Caffrey,Samuel H. Gellman,Jan Steyaert,Jan Steyaert,Georgios Skiniotis,William I. Weis,Roger K. Sunahara,Brian K. Kobilka +21 more