Takeda Soichi
Department of Cardiac Physiology, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Semin Cell Dev Biol. 2009 Apr;20(2):146-52. doi: 10.1016/j.semcdb.2008.07.009. Epub 2008 Jul 26.
A disintegrin and metalloproteinase (ADAM) family of proteins constitutes a major class of mammalian membrane-bound sheddases that are responsible for the processing of cell-surface-protein ectodomains, including the latent forms of growth factors, cytokines and their receptors. However, the molecular mechanism by which ADAMs recognize and process their substrates is largely unknown. Recent crystallographic studies on phylogenically related snake venom metalloproteinases (SVMPs) and mammalian ADAM with thrombospondin type-1 motif (ADAMTS) family proteins have shed light on the structure-function properties of ADAMs. This review will highlight these recent structures, particularly the non-catalytic ancillary domains, which might be important for substrate recognition.
解聚素和金属蛋白酶(ADAM)家族蛋白是哺乳动物膜结合型蛋白酶的主要类别,负责处理细胞表面蛋白的胞外结构域,包括生长因子、细胞因子及其受体的潜在形式。然而,ADAM识别和处理其底物的分子机制在很大程度上尚不清楚。最近对系统发育相关的蛇毒金属蛋白酶(SVMP)和具有血小板反应蛋白1型基序的哺乳动物ADAM(ADAMTS)家族蛋白的晶体学研究,揭示了ADAM的结构-功能特性。本综述将重点介绍这些最新结构,特别是非催化辅助结构域,它们可能对底物识别很重要。