Head James F, Swamy Narasimha, Ray Rahul
Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Biochemistry. 2002 Jul 23;41(29):9015-20. doi: 10.1021/bi026054y.
A high-affinity complex formed between G-actin and plasma vitamin D-binding protein (DBP) is believed to form part of a scavenging system in the plasma for removing actin released from damaged cells. In the study presented here, we describe the crystal structure of the complex between actin and human vitamin D-binding protein at 2.5 A resolution. The complex contains one molecule of each protein bound together by extensive ionic, polar, and hydrophobic interactions. It includes an ATP and a calcium ion bound to actin, but no evidence of vitamin D metabolites bound to the DBP. Both actin and DBP are multidomain molecules, two major domains in actin and three in DBP. All of these domains contribute to the interaction between the molecules. DBP enfolds the end of the actin molecule, principally in actin subdomain 3 but with additional interactions in actin subdomain 1. This orientation is similar to the binding of profilin to actin, as predicted from previous studies. The more extensive interactions of DBP give an affinity for actin some 3 orders of magnitude higher than that for profilin. The larger "footprint" of DBP on actin also leads to an overlap with the actin-binding site of gelsolin domain I.
G-肌动蛋白与血浆维生素D结合蛋白（DBP）之间形成的高亲和力复合物被认为是血浆中清除受损细胞释放的肌动蛋白的清除系统的一部分。在本文所述的研究中，我们描述了肌动蛋白与人类维生素D结合蛋白之间复合物的晶体结构，分辨率为2.5埃。该复合物包含通过广泛的离子、极性和疏水相互作用结合在一起的每种蛋白质的一个分子。它包括一个与肌动蛋白结合的ATP和一个钙离子，但没有证据表明维生素D代谢物与DBP结合。肌动蛋白和DBP都是多结构域分子，肌动蛋白有两个主要结构域，DBP有三个主要结构域。所有这些结构域都参与了分子间的相互作用。DBP包裹着肌动蛋白分子的末端，主要在肌动蛋白亚结构域3，但在肌动蛋白亚结构域1也有额外的相互作用。正如先前研究所预测的，这种取向类似于profilin与肌动蛋白的结合。DBP更广泛的相互作用使其对肌动蛋白的亲和力比profilin高约3个数量级。DBP在肌动蛋白上更大的“足迹”也导致其与凝溶胶蛋白结构域I的肌动蛋白结合位点重叠。
