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-Structure paper
タイトル | Platelet integrin αIIbβ3 plays a key role in a venous thrombogenesis mouse model. |
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ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 8612, Year 2024 |
掲載日 | 2024年10月4日 |
![]() | Brian D Adair / Conroy O Field / José L Alonso / Jian-Ping Xiong / Shi-Xian Deng / Hyun Sook Ahn / Eivgeni Mashin / Clary B Clish / Johannes van Agthoven / Mark Yeager / Youzhong Guo / David A Tess / Donald W Landry / Mortimer Poncz / M Amin Arnaout / ![]() |
PubMed 要旨 | Venous thrombosis (VT) is a common vascular disease associated with reduced survival and a high recurrence rate. VT is initiated by the accumulation of platelets and neutrophils at sites of ...Venous thrombosis (VT) is a common vascular disease associated with reduced survival and a high recurrence rate. VT is initiated by the accumulation of platelets and neutrophils at sites of endothelial cell activation. A role for platelet αIIbβ3 in VT is not established, a task complicated by the increased bleeding risk caused by partial agonists such as tirofiban. Here, we show that m-tirofiban, a modified version of tirofiban, does not agonize αIIbβ3 based on lack of neoepitope expression and the cryo-EM structure of m-tirofiban/full-length αIIbβ3 complex. m-tirofiban abolishes agonist-induced platelet aggregation while preserving clot retraction ex vivo and, unlike tirofiban, it suppresses venous thrombogenesis in a mouse model without increasing bleeding. These findings establish a key role for αIIbβ3 in VT initiation and suggest that m-tirofiban and compounds with a similar structurally-defined mechanism of action merit consideration as potential thromboprophylaxis agents in patients at high risk for VT and hemorrhage. |
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手法 | EM (単粒子) |
解像度 | 3.9 - 4.1 Å |
構造データ | EMDB-46793, PDB-9deq: EMDB-46794, PDB-9der: |
化合物 | ![]() ChemComp-CA: ![]() ChemComp-NAG: ![]() ChemComp-MG: ![]() PDB-1a5g: ![]() ChemComp-CLR: ![]() ChemComp-HOH: ![]() ChemComp-AGG: |
由来 |
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![]() | CELL ADHESION / complex / open headpiece |