Journal ArticleDOI
The G-Protein-Coupled Receptors in the Human Genome Form Five Main Families : Phylogenetic Analysis, Paralogon Groups, and Fingerprints
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TLDR
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.Abstract:
The superfamily of G-protein-coupled receptors (GPCRs) is very diverse in structure and function and its members are among the most pursued targets for drug development. We identified more than 800 human GPCR sequences and simultaneously analyzed 342 unique functional nonolfactory human GPCR sequences with phylogenetic analyses. Our results show, with high bootstrap support, five main families, named glutamate, rhodopsin, adhesion, frizzled/taste2, and secretin, forming the GRAFS classification system. The rhodopsin family is the largest and forms four main groups with 13 sub-branches. Positions of the GPCRs in chromosomal paralogons regions indicate the importance of tetraploidizations or local gene duplication events for their creation. We also searched for "fingerprint" motifs using Hidden Markov Models delineating the putative inter-relationship of the GRAFS families. We show several common structural features indicating that the human GPCRs in the GRAFS families share a common ancestor. This study represents the first overall map of the GPCRs in a single mammalian genome. Our novel approach of analyzing such large and diverse sequence sets may be useful for studies on GPCRs in other genomes and divergent protein families.read more
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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
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.
Journal ArticleDOI
The structure and function of G-protein-coupled receptors
TL;DR: G-protein-coupled receptors mediate most of the authors' physiological responses to hormones, neurotransmitters and environmental stimulants, and so have great potential as therapeutic targets for a broad spectrum of diseases.
Journal ArticleDOI
Transduction of receptor signals by beta-arrestins.
TL;DR: Another previously unappreciated strategy used by the receptors to regulate intracellular signaling pathways is indicated, which regulates aspects of cell motility, chemotaxis, apoptosis, and likely other cellular functions through a rapidly expanding list of signaling pathways.
Journal ArticleDOI
The genome sequence of the rice blast fungus Magnaporthe grisea
Ralph A. Dean,Nicholas J. Talbot,Daniel J. Ebbole,Mark L. Farman,Thomas K. Mitchell,Marc J. Orbach,Michael R. Thon,Resham Kulkarni,Resham Kulkarni,Jin-Rong Xu,Huaqin Pan,Nick D. Read,Yong-Hwan Lee,Ignazio Carbone,Doug Brown,Yeonyee Oh,Nicole M. Donofrio,Jun Seop Jeong,Darren M. Soanes,Slavica Djonovic,Elena A. Kolomiets,Cathryn J. Rehmeyer,Weixi Li,Michael W. Harding,Soonok Kim,Marc-Henri Lebrun,Heidi U. Böhnert,Sean J. Coughlan,Jonathan Butler,Sarah E. Calvo,Li-Jun Ma,Robert Nicol,Seth Purcell,Chad Nusbaum,James E. Galagan,Bruce W. Birren +35 more
TL;DR: The draft sequence of the M. grisea genome is reported, reflecting the clonal nature of this fungus imposed by widespread rice cultivation and analysis of the gene set provides an insight into the adaptations required by a fungus to cause disease.
References
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TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Journal ArticleDOI
The sequence of the human genome.
J. Craig Venter,Mark Raymond Adams,Eugene W. Myers,Peter W. Li,Richard J. Mural,Granger G. Sutton,Hamilton O. Smith,Mark Yandell,Cheryl A. Evans,Robert A. Holt,Jeannine D. Gocayne,Peter Amanatides,Richard M. Ballew,Daniel H. Huson,Jennifer R. Wortman,Qing Zhang,Chinnappa D. Kodira,Xiangqun H. Zheng,Lin Chen,Marian P. Skupski,Gangadharan Subramanian,Paul Thomas,Jinghui Zhang,George L. Gabor Miklos,Catherine R. Nelson,Samuel Broder,Andrew G. Clark,J. H. Nadeau,Victor A. McKusick,Norton D. Zinder,Arnold J. Levine,Richard J. Roberts,M. I. Simon,Carolyn W. Slayman,Michael W. Hunkapiller,Randall Bolanos,Arthur L. Delcher,Ian M. Dew,Daniel Fasulo,Michael Flanigan,Liliana Florea,Aaron L. Halpern,Sridhar Hannenhalli,Saul A. Kravitz,Samuel Levy,Clark M. Mobarry,Knut Reinert,Karin A. Remington,Jane Abu-Threideh,Ellen M. Beasley,Kendra Biddick,Vivien Bonazzi,Rhonda Brandon,Michele Cargill,Ishwar Chandramouliswaran,Rosane Charlab,Kabir Chaturvedi,Zuoming Deng,Valentina Di Francesco,Patrick Dunn,Karen Eilbeck,Carlos Evangelista,Andrei Gabrielian,Weiniu Gan,Wangmao Ge,Fangcheng Gong,Zhiping Gu,Ping Guan,Thomas J. Heiman,Maureen E. Higgins,Rui-Ru Ji,Zhaoxi Ke,Karen A. Ketchum,Zhongwu Lai,Yiding Lei,Zhenya Li,Jiayin Li,Yong Liang,Xiaoying Lin,Fu Lu,Gennady V. Merkulov,Natalia Milshina,Helen M. Moore,Ashwinikumar K Naik,Vaibhav A. Narayan,Beena Neelam,Deborah Nusskern,Douglas B. Rusch,Steven L. Salzberg,Wei Shao,Bixiong Chris Shue,Jingtao Sun,Zhen Yuan Wang,Aihui Wang,Xin Wang,Jian Wang,Ming-Hui Wei,Ron Wides,Chunlin Xiao,Chunhua Yan,Alison Yao,Jane Ye,Ming Zhan,Weiqing Zhang,Hongyu Zhang,Qi Zhao,Liansheng Zheng,Fei Zhong,Wenyan Zhong,Shiaoping C. Zhu,Shaying Zhao,Dennis A. Gilbert,Suzanna Baumhueter,Gene Spier,Christine Carter,Anibal Cravchik,Trevor Woodage,Feroze Ali,Huijin An,Aderonke Awe,Danita Baldwin,Holly Baden,Mary Barnstead,Ian Barrow,Karen Beeson,Dana A. Busam,Amy Carver,Ming Lai Cheng,Liz Curry,Steve Danaher,Lionel Davenport,Raymond Desilets,Susanne Dietz,Kristina Dodson,Lisa Doup,Steven Ferriera,Neha Garg,Andres Gluecksmann,Brit J. Hart,Jason Haynes,Charles Haynes,Cheryl Heiner,Suzanne Hladun,Damon Hostin,Jarrett Houck,Timothy Howland,Chinyere Ibegwam,Jeffery Johnson,Francis Kalush,Lesley Kline,Shashi Koduru,Amy Love,Felecia Mann,David May,Steven McCawley,Tina C. McIntosh,Ivy McMullen,Mee Moy,Linda Moy,Brian Murphy,Keith Nelson,Cynthia Pfannkoch,Eric Pratts,Vinita Puri,Hina Qureshi,Matthew Reardon,Robert Rodriguez,Yu-Hui Rogers,Deanna Romblad,Bob Ruhfel,Richard T. Scott,Cynthia Sitter,Michelle Smallwood,Erin Stewart,Renee Strong,Ellen Suh,Reginald Thomas,Ni Ni Tint,Sukyee Tse,Claire Vech,Gary Wang,Jeremy Wetter,Sherita Williams,Monica Williams,Sandra Windsor,Emily Winn-Deen,Keriellen Wolfe,Jayshree Zaveri,Karena Zaveri,Josep F. Abril,Roderic Guigó,Michael J. Campbell,Kimmen Sjölander,Brian Karlak,Anish Kejariwal,Huaiyu Mi,Betty Lazareva,Thomas Hatton,Apurva Narechania,Karen Diemer,Anushya Muruganujan,Nan Guo,Shinji Sato,Vineet Bafna,Sorin Istrail,Ross Lippert,Russell Schwartz,Brian P. Walenz,Shibu Yooseph,David Allen,Anand Basu,James Baxendale,Louis Blick,Marcelo Caminha,John Carnes-Stine,Parris Caulk,Yen-Hui Chiang,My Coyne,Carl Dahlke,Anne Deslattes Mays,Maria Dombroski,Michael Donnelly,Dale Ely,Shiva Esparham,Carl Fosler,Harold Gire,Stephen Glanowski,Kenneth Glasser,Anna Glodek,Mark Gorokhov,Ken Graham,Barry Gropman,Michael Harris,Jeremy Heil,Scott Henderson,Jeffrey Hoover,Donald Jennings,Catherine Jordan,James Jordan,John Kasha,Leonid Kagan,Cheryl L. Kraft,Alexander Levitsky,Mark Lewis,Xiangjun Liu,John Lopez,Daniel Ma,William H. Majoros,Joe McDaniel,Sean C. Murphy,Matthew Newman,Trung Hieu Nguyen,Ngoc Nguyen,Marc Nodell,Sue Pan,Jim Peck,Marshall Peterson,William Rowe,Robert Sanders,John Scott,Michael Simpson,Thomas J. Smith,Arlan Sprague,Timothy B. Stockwell,Russell Turner,Eli Venter,Mei Wang,Meiyuan Wen,David Wu,Mitchell Wu,Ashley Xia,Ali Zandieh,Xiaohong Zhu +272 more
TL;DR: Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems are indicated.
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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