2012 Fiscal Year Final Research Report
Challenges for the structure determination of GPCR active conformation
| Project/Area Number |
23657074
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Structural biochemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
OGASAWARA Satoshi 京都大学, 医学研究科, 研究員 (30546685)
ASADA Hidetsugu 京都大学, 医学研究科, 研究員 (20399041)
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| Project Period (FY) |
2011 – 2012
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| Keywords | X線結晶解析 / 受容体 / GPCR / 膜タンパク質 |
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| Research Abstract |
In order to understand the GPCR-mediated signal transduction mechanisms, it is essential to determine the GPCR structures in the active and inactive conformations. We published the structure of Histamine H1 receptor in complex with an inverse agonist doxepin. The structure revealed the reason why doxepin shows high affinities to aminergic receptors. We also published the structure of Adenosine A2a receptor in the inactive conformation. For crystallization, the receptor was stabilized in the inactive conformation by the binding of Fab fragment. The antibody that stabilizes the receptor in the active conformation was successfully obtained. This antibody will be useful for the determination of the Adenosine A2a receptor structure in the active conformation.
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Research Products
(22 results)
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[Journal Article] Platform for the rapidconstruction and evaluation of GPCRs forcrystallography in Saccharomycescerevisiae.2012
Author(s)
Shiroishi M, Tsujimoto H, Makyio H, Asada H, Yurugi-Kobayashi T, Shimamura T, Murata T, Nomura N, Haga T, Iwata S, Kobayashi T.
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Journal Title
Microb Cell Fact.
Volume: 11
Pages: 78
DOI
Peer Reviewed
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[Journal Article] G-protein-coupled receptor inactivation by anallosteric inverse-agonist antibody.2012
Author(s)
Hino T, Arakawa T, Iwanari H, Yurugi-Kobayashi T, Ikeda-Suno C, Nakada-Nakura Y, Kusano-Arai O, Weyand S, Shimamura T, Nomura N, Cameron AD, Kobayashi T,Hamakubo T, Iwata S, Murata T.
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Journal Title
Nature.
Volume: 482(7384)
Pages: 237-40
DOI
Peer Reviewed
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[Journal Article] Crystal structure-based virtual screening for fragment-like ligands of the human histamine H(1) receptor.2011
Author(s)
de Graaf C, Kooistra AJ, Vischer HF, Katritch V, Kuijer M, Shiroishi M, Iwata S, Shimamura T, Stevens RC, de Esch IJ, Leurs R.
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Journal Title
J Med Chem.
Volume: 54(23)
Pages: 8195-206
DOI
Peer Reviewed
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[Journal Article] Structure of the human histamine H1 receptor complex with doxepin.2011
Author(s)
Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, AbagyanR, Cherezov V, Liu W, Han GW, Kobayashi T, Stevens RC, Iwata S.
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Journal Title
Nature
Volume: 475 (7354)
Pages: 65-70
DOI
Peer Reviewed
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[Journal Article] Cloning,expression and purification of the anion exchanger 1 homologue from thebasidiomycetePhanerochaete chrysosporium.2011
Author(s)
Tokuda N, Igarashi K, Shimamura T, Yurugi-Kobayashi T, Shiroishi M, Ito K,Sugawara T, Asada H, Murata T, Nomura N, Iwata S, Kobayashi T.
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Journal Title
Protein Expr Purif.
Volume: 79(1)
Pages: 81-7
DOI
Peer Reviewed
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