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标题：Solution structures of the cytoplasmic tail complex from platelet integrin αIIb- and β3-subunits
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作者：Aalim M. Weljie ; Peter M. Hwang ; Hans J. Vogel 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：9
页码：5878-5883
DOI：10.1073/pnas.092515799
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Integrin adhesion receptors constitute a cell-signaling system whereby interactions in the small cytoplasmic domains of the heterodimeric - and {beta}-subunits provoke major functional alterations in the large extracellular domains. With two-dimensional NMR spectroscopy, we examined two synthetic peptides [IIb(987MWKVGFFKRNR) and {beta}3(716KLLITIHDRKEFAKFEEERARAKWD)] encompassing the membrane-proximal regions of the cytoplasmic domain motifs from the platelet integrin complex IIb{beta}3. These membrane-proximal regions contain two conserved motifs, represented by 989KVGFFKR in the IIb-subunit, and 716KLLITIHDR in the {beta}3-subunit. The dimer interaction consists of two adjacent helices with residues V990 and F993 of the IIb-subunit heavily implicated in the dimer interfacial region, as is I719 of {beta}3. These residues are situated within the conserved motifs of their respective proteins. Further structural analysis of this unique peptide heterodimer suggests that two distinct conformers are present. The major structural difference between the two conformers is a bend in the {beta}3-peptide between D723 and A728, whereas the helical character in the other regions remains intact. Earlier mutational analysis has shown that a salt bridge between the side chains of IIb(R955) and {beta}3(D723) is formed. When this ion pair was modeled into both conformers, increased nuclear Overhauser effect violations suggested that the more bent structure was less able to accommodate this interaction. These results provide a molecular level rationalization for previously reported biochemical studies, as well as a basis for an atomic level understanding of the intermolecular interactions that regulate integrin activity.