Details of a Researcher - Kamata, Tetsuji

Paolo Gresele, Valentin Fuster, Jose A. Lopez, Clive P. Page, Jos Vermylen, eds. PLATELETS IN HEMATOLOGIC AND CARDIOVASCULAR DISORDERS: A CLINICAL HANDBOOK

Yasuo Ikeda, Yumiko Matsubara, Kamata Tetsuji, Cambridge University Press, 2008

Scope: Platelet immunology: structure, functions, and polymorphisms of membrane glycoproteins
血栓症ナビゲータ

鎌田徹治, メディカルレビュー社, 2005

Scope: 細胞外基質
池田康夫編集「血小板生物学」

鎌田徹治, メディカルレビュー社, 2004

Scope: 血小板インテグリン−β１インテグリン
最新内科学体系２１

池田康夫，鎌田徹治, 中山書店, 1992

Scope: 先天性血小板機能異常症

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Papers 【 Display / hide 】

Electron microscopy shows that binding of monoclonal antibody PT25-2 primes integrin αIIbβ3 for ligand binding

Nesi D., Bush M., Coller B.S., Li J., Kamata T., Handa M., Walz T.

Blood Advances （Blood Advances) 5 （ 7 ） 1781 - 1790 2021.03

ISSN 24739529

　View Summary

The murine monoclonal antibody (mAb) PT25-2 induces aIIbβ3 to bind ligand and initiate platelet aggregation. The underlying mechanism is unclear, because previous mutagenesis studies suggested that PT25-2 binds to the aIIb b propeller, a site distant from the Arg-Gly-Asp-binding pocket. To elucidate the mechanism, we studied the aIIbb3-PT25-2 Fab complex by negative-stain and cryo-electron microscopy (EM). We found that PT25-2 binding results in aIIbb3 partially exposing multiple ligand-induced binding site epitopes and adopting extended conformations without swing-out of the b3 hybrid domain. The cryo-EM structure showed PT25-2 binding to the aIIb residues identified by mutagenesis but also to 2 additional regions. Overlay of the cryo-EM structure with the bent aIIbb3 crystal structure showed that binding of PT25-2 creates clashes with the aIIb calf-1/calf-2 domains, suggesting that PT25-2 selectively binds to partially or fully extended receptor conformations and prevents a return to its bent conformation. Kinetic studies of the binding of PT25-2 compared with mAbs 10E5 and 7E3 support this hypothesis. We conclude that PT25-2 induces aIIbb3 ligand binding by binding to extended conformations and by preventing the interactions between the aIIb and b3 leg domains and subsequently the bI and b3 leg domains required for the bent-closed conformation.
- Access to Document (DOI)
Epitope mapping for monoclonal antibody reveals the activation mechanism for αVβ3 integrin

Kamata T, Handa M, Takakuwa S, Sato Y, Kawai Y, Ikeda Y, Aiso S

PLoS One 8 （ 6 ） e66096 2013

Research paper (scientific journal), Joint Work, Accepted
Structural requirements for activation in alphaIIb beta3 integrin

Kamata T, Handa M, Ito S, Sato Y, Ohtani T, Kawai Y, Ikeda Y, Aiso S

J Biol Chem 285 （ 49 ） 38428 - 38437 2010

Research paper (scientific journal), Joint Work, Accepted
Key interactions in integrin ectodomain responsible for global conformational change detected by elastic network normal-mode analysis

Matsumoto A, Kamata T, Takagi J, Iwasaki K, Yura K

Biophys J 95 （ 6 ） 2895 - 2908 2008

Research paper (scientific journal), Joint Work, Accepted
血小板β１インテグリン

鎌田徹治

医学のあゆみ 2005

Research paper (scientific journal), Single Work, Accepted

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Presentations 【 Display / hide 】

Divalent cations define the structural requirement for activation in αIIbβ3 integrin

Kamata T, Handa M, Kawai Y, Ikeda Y, Aiso S

The 54th ASH Annual Meeting and Exposition (Atlanta, GA, USA) ,

2012.12
Separation of the two extracellular tails is required to propagate activation signals initiated in the cytoplasmic tails of αIIbβ3 integrin

Kamata T, Handa M, Kawai Y, Ikeda Y, Aiso S

The 23rd Congress of the International Society on Thrombosis and Haemostasis (Kyoto, Japan) ,

2011.07
Regulatory Role of the Extracellular α-tail/β-tail Interaction in αIIbβ3 Integrin Activation

Kamata T, Handa M, Kawai Y, Ikeda Y, Aiso S

The 52nd American Society of Hematology Annual Meeting and Exposition (Orlando, Florida, USA) ,

2010.12
血小板 αIIbβ3　インテグリンの活性化メカニズム

鎌田徹治

第17回日本血液代替物学会年次大会シンポジウム (熊本市国際交流会館，熊本市) ,

2010.10
細胞外α-tail/β-tail の結合はαIIbβ3インテグリンの活性化を制御する

鎌田徹治，半田　誠，川合陽子，池田康夫，相磯貞和

第72回日本血液学会学術集会一般口演 (パシフィコ横浜，横浜市西区みなとみらい) ,

2010.09