Gorbatyuk Vitaliy, Nguyen Khiem, Podolnikova Nataly P, Deshmukh Lalit, Lin Xiaochen, Ugarova Tatiana P, Vinogradova Olga
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut at Storrs , Storrs, Connecticut 06269, United States.
Biochemistry. 2014 Nov 4;53(43):6766-75. doi: 10.1021/bi500680s. Epub 2014 Oct 22.
Over the last two decades, our knowledge concerning intracellular events that regulate integrin's affinity to their soluble ligands has significantly improved. However, the mechanism of adhesion-induced integrin clustering and development of focal complexes, which could further mature to form focal adhesions, still remains under-investigated. Here we present a structural model of tandem IgC2 domains of skelemin in complex with the cytoplasmic tails of integrin αIIbβ3. The model of tertiary assembly is generated based upon NMR data and illuminates a potential link between the essential cell adhesion receptors and myosin filaments. This connection may serve as a basis for generating the mechanical forces necessary for cell migration and remodeling.
在过去二十年中，我们对于调节整合素与可溶性配体亲和力的细胞内事件的了解有了显著提高。然而，粘附诱导的整合素聚集以及粘着斑复合物的形成机制（粘着斑复合物可进一步成熟形成粘着斑）仍研究不足。在此，我们展示了与整合素αIIbβ3细胞质尾部结合的skelemin串联IgC2结构域的结构模型。三级组装模型基于核磁共振数据生成，揭示了关键细胞粘附受体与肌球蛋白丝之间的潜在联系。这种联系可能是产生细胞迁移和重塑所需机械力的基础。
