Targeting platelet-leukocyte interactions: identification of the integrin Mac-1 binding site for the platelet counter receptor glycoprotein Ibalpha.
Targeting platelet-leukocyte interactions: identification of the integrin Mac-1 binding site for the platelet counter receptor glycoprotein Ibalpha.
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靶向血小板 - 白细胞相互作用：鉴定血小板计数器受体糖蛋白IBALPHA的整联蛋白MAC-1结合位点。
DOI：
10.1084/jem.20022181
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发表时间：
2003-10-06
期刊：
影响因子：
--
通讯作者：
Simon DI
中科院分区：
文献类型：
--
作者：
Ehlers R;Ustinov V;Chen Z;Zhang X;Rao R;Luscinskas FW;Lopez J;Plow E;Simon DI
白细胞在血栓表面的粘附和跨血小板迁移依赖于白细胞整合素Mac-1（αMβ2，CD 11b/CD 18）和血小板反受体糖蛋白（GP）Ibα的相互作用。先前的研究已经确定了I结构域在GP Ibα结合中的中心作用，I结构域是αM亚基内的一段约200个氨基酸。本研究旨在建立αMβ2识别GP Ibα的分子基础。P201-K217序列跨越αMI结构域三维结构中的一个暴露环和两亲性α4螺旋，被鉴定为GP Ibα的结合位点。突变细胞系中，αMI结构域片段P201-G207和R208-K217被转换为同源的但非GP Ibα结合的αL结构域片段，不能支持与GP Ibα的粘附。P201-K217、H210-A212、T213-I215和R216-K217中氨基酸残基的突变导致重组αMI结构域与GP Ibα结合功能的丧失。复制P201-K217的合成肽，而不是乱序形式，直接结合GP Ibα并抑制αMβ2依赖性粘附于GP Ibα和粘附血小板。最后，将P201-K217序列中的关键氨基酸移植到αL上，将αLβ2转化为GP Ibα结合整联蛋白。因此，αMI结构域中的P201-K217序列对于GP Ibα结合是必需的和充分的。这些观察结果提供了一个分子靶点，破坏白细胞-血小板复合物，促进血栓形成，动脉粥样硬化和血管成形术相关的再狭窄的血管炎症。
The firm adhesion and transplatelet migration of leukocytes on vascular thrombus are dependent on the interaction of the leukocyte integrin Mac-1 (αMβ2, CD11b/CD18) and the platelet counter receptor glycoprotein (GP) Ibα. Previous studies have established a central role for the I domain, a stretch of ∼200 amino acids within the αM subunit, in the binding of GP Ibα. This study was undertaken to establish the molecular basis of GP Ibα recognition by αMβ2. The P201–K217 sequence, which spans an exposed loop and amphipathic α4 helix in the three-dimensional structure of the αMI domain, was identified as the binding site for GP Ibα. Mutant cell lines in which the αMI domain segments P201–G207 and R208–K217 were switched to the homologous, but non-GP Ibα binding, αL domain segments failed to support adhesion to GP Ibα. Mutation of amino acid residues within P201–K217, H210–A212, T213–I215, and R216–K217 resulted in the loss of the binding function of the recombinant αMI domains to GP Ibα. Synthetic peptides duplicating the P201–K217, but not scrambled versions, directly bound GP Ibα and inhibited αMβ2-dependent adhesion to GP Ibα and adherent platelets. Finally, grafting critical amino acids within the P201–K217 sequence onto αL, converted αLβ2 into a GP Ibα binding integrin. Thus, the P201–K217 sequence within the αMI domain is necessary and sufficient for GP Ibα binding. These observations provide a molecular target for disrupting leukocyte–platelet complexes that promote vascular inflammation in thrombosis, atherosclerosis, and angioplasty-related restenosis.
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影响因子：
7.8
作者：
DIAMOND, MS;ALON, R;SPRINGER, TA
通讯作者：
SPRINGER, TA
DOI：
10.1083/jcb.125.6.1417
发表时间：
1994-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Luscinskas FW;Kansas GS;Ding H;Pizcueta P;Schleiffenbaum BE;Tedder TF;Gimbrone MA Jr
通讯作者：
Gimbrone MA Jr
DOI：
10.1073/pnas.85.20.7462
发表时间：
1988-10-01
影响因子：
11.1
作者：
ALTIERI, DC;MORRISSEY, JH;EDGINGTON, TS
通讯作者：
EDGINGTON, TS
DOI：
10.1073/pnas.92.5.1505
发表时间：
1995-02-28
影响因子：
11.1
作者：
LANGUINO, LR;DUPERRAY, A;ALTIERI, DC
通讯作者：
ALTIERI, DC
影响因子：
4.8
作者：
Rieu, P;Sugimori, T;Arnaout, MA
通讯作者：
Arnaout, MA