文章基本信息

标题：Cross-linking reveals laminin coiled-coil architecture
本地全文：下载
作者：Gad Armony ; Etai Jacob ; Toot Moran 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：2016
卷号：113
期号：47
页码：13384-13389
DOI：10.1073/pnas.1608424113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceLarge, fibrous, and flexible extracellular matrix proteins are integral to development and maintenance of tissues in the body. Laminin is an extracellular matrix component that provides a physical substrate for cell adhesion and induces signaling pathways that maintain cell health and functionality. Despite the physiological importance of laminin, major gaps remain in our understanding of how its three subunits come together to form the characteristic cross-shaped laminin structure. Laminin was treated with chemicals that link amino acids close in space, providing a map of the subunit arrangement and correcting previous suppositions made on the basis of amino acid sequence inspection alone. Laminin, an [~]800-kDa heterotrimeric protein, is a major functional component of the extracellular matrix, contributing to tissue development and maintenance. The unique architecture of laminin is not currently amenable to determination at high resolution, as its flexible and narrow segments complicate both crystallization and single-particle reconstruction by electron microscopy. Therefore, we used cross-linking and MS, evaluated using computational methods, to address key questions regarding laminin quaternary structure. This approach was particularly well suited to the [~]750-[IMG]f1.gif" ALT="A" BORDER="0"> coiled coil that mediates trimer assembly, and our results support revision of the subunit order typically presented in laminin schematics. Furthermore, information on the subunit register in the coiled coil and cross-links to downstream domains provide insights into the self-assembly required for interaction with other extracellular matrix and cell surface proteins.
关键词：coiled coil ; extracellular matrix ; laminin ; cross-linking ; mass spectrometry