Jenner L, Husted L, Thirup S, Sottrup-Jensen L, Nyborg J
Department of Molecular and Structural Biology, University of Aarhus, Denmark.
Structure. 1998 May 15;6(5):595-604. doi: 10.1016/s0969-2126(98)00061-6.
The large plasma proteinase inhibitors of the alpha 2-macroglobulin superfamily inhibit proteinases by capturing them within a central cavity of the inhibitor molecule. After reaction with the proteinase, the alpha-macroglobulin-proteinase complex binds to the alpha-macroglobulin receptor, present in the liver and other tissues, and becomes endocytosed and rapidly removed from the circulation. The complex binds to the receptor via recognition sites located on a separate domain of approximately 138 residues positioned at the C terminus of the alpha-macroglobulin subunit.
The crystal structure of the receptor-binding domain of bovine alpha 2-macroglobulin (bRBD) has been determined at a resolution of 1.9 A. The domain primarily comprises a nine-strand beta structure with a jelly-roll topology, but also contains two small alpha helices.
The surface patch responsible for receptor recognition is thought to involve residues located on one of the two alpha helices of the bRBD as well as residues in two of the beta strands. Located on this alpha helix are two lysine residues that are important for receptor binding. The structure of bRBD is very similar to the approximately 100-residue C-terminal domain of factor XIII, a transglutaminase from the blood coagulation system.
α2-巨球蛋白超家族的大型血浆蛋白酶抑制剂通过将蛋白酶捕获在抑制剂分子的中央腔中来抑制蛋白酶。与蛋白酶反应后，α-巨球蛋白-蛋白酶复合物与肝脏和其他组织中存在的α-巨球蛋白受体结合，被内吞并迅速从循环中清除。该复合物通过位于α-巨球蛋白亚基C末端约138个残基的单独结构域上的识别位点与受体结合。
已确定牛α2-巨球蛋白（bRBD）受体结合结构域的晶体结构，分辨率为1.9 Å。该结构域主要由具有果冻卷拓扑结构的九股β结构组成，但也包含两个小的α螺旋。
负责受体识别的表面区域被认为涉及bRBD的两个α螺旋之一上的残基以及两条β链中的残基。位于该α螺旋上的两个赖氨酸残基对受体结合很重要。bRBD的结构与来自血液凝固系统的转谷氨酰胺酶因子XIII的约100个残基的C末端结构域非常相似。
