Structural basis for integrin alphaIIbbeta3 clustering.
Structural basis for integrin alphaIIbbeta3 clustering.
复制标题
整合素 αIIbbeta3 聚类的结构基础。
DOI：
10.1042/bst0320412
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发表时间：
2004
影响因子：
3.9
通讯作者：
Degrado,WF
中科院分区：
文献类型：
--
作者：
Li,R;Bennett,JS;Degrado,WF
我们表达了两种与整合素αIIb和β3亚基的跨膜和细胞质结构域相对应的蛋白质。对分散在阴离子和两性离子胶束中的这些蛋白质的表征表明，这两种蛋白质不是彼此相互作用，而是分别缔合成同型二聚体和同型三聚体。此外，使用 TOXCAT 检测系统的研究证实，αIIb 和 β3 跨膜结构域可以在生物细胞膜中自我关联。跨膜结构域介导的同源寡聚化为整合素聚类提供了合理的结构基础，并且也可以促进整合素激活。事实上，用天冬酰胺残基替换 αIIb 或 β3 跨膜螺旋中的特定残基会促进突变跨膜螺旋的同源寡聚化，促进细胞表面整合素簇的形成，并将 αIIbβ3 转变为激活状态。因此，这些研究支持跨膜结构域在 αIIbβ3 的功能和调节中发挥重要作用的假设。
We have expressed two proteins that correspond to the transmembrane and cytoplasmic domains of integrin αIIb and β3 subunits. Characterization of these proteins, dispersed in anionic and zwitterionic micelles, revealed that, rather than interacting with each other, the two proteins associated into homodimers and homotrimers respectively. Moreover, studies using the TOXCAT assay system confirmed that the αIIb and β3 transmembrane domains can self-associate in biological cell membranes. Transmembrane domain-mediated homo-oligomerization provides a plausible structural basis for integrin clustering and could promote integrin activation as well. Indeed, replacing specific residues in the transmembrane helix of either αIIb or β3 with an asparagine residue resulted in a facilitated homo-oligomerization of the mutated transmembrane helix, promoted the formation of integrin clusters on the cell surface and shifted αIIbβ3 to its activated state. Thus these studies support the hypothesis that the transmembrane domains play a vital role in the function and regulation of αIIbβ3.