The Crystal Structures of Human S100A12 in Apo Form and in Complex with Zinc: New Insights into S100A12 Oligomerisation
The Crystal Structures of Human S100A12 in Apo Form and in Complex with Zinc: New Insights into S100A12 Oligomerisation
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DOI：
10.1016/j.jmb.2009.06.004
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发表时间：
2009-08-21
影响因子：
5.6
通讯作者：
Bronstein, Igor B.
中科院分区：
文献类型：
--
作者：
Moroz, Olga V.;Blagova, Elena V.;Bronstein, Igor B.
EF-手蛋白的S100家族成员的功能由钙调节，并且在许多情况下由锌或铜调节。一种这样的蛋白质是S100 A12，它与炎症和宿主-寄生虫反应有关。在此之前，我们报道了人S100 A12的结构，低（二聚体）和高（六聚体）钙的形式，此外，与铜和钙的复合物。在这里，我们报告的晶体结构的无金属载脂蛋白形式的人S100 A12在1.77埃分辨率和锌络合物的两种晶体形式（P2（1）2（1）2（1）和F222），分别为1.88埃和1.73埃分辨率。这些是S100蛋白的仅含锌复合物的第一个结构。锌络合物结构显示出显着的差异，从钙负载和apo-S100 A12结构，和比较表明锌诱导的钙亲和力增加1500倍的解释。此外，新的结构提供了深入了解锌-钙相互作用的作用，在过渡的S100 A12从二聚体通过四聚体到六聚体。锌和钙在宿主-寄生虫反应过程中S100 A12靶结合中的作用通过热带寄生虫盘尾丝虫和马来丝虫的副肌球蛋白实验得到证实。(C)2009爱思唯尔有限公司保留所有权利。
The functions of the members of the S100 family of EF-hand proteins are modulated by calcium and, in a number of cases, by zinc or copper. One such protein is S100A12, which is implicated in inflammation and host-parasite responses. Previously, we reported the structures of human S100A12 in both low (dimeric) and high (hexameric) calcium forms and, in addition, that of a complex with copper and calcium. Here we report the crystal structures of the metal-free apo form of human S100A12 at 1.77 angstrom resolution and of the zinc complex in two crystal forms (P2(1)2(1)2(1) and F222) to 1.88 angstrom and 1.73 angstrom resolution, respectively. These are the first structures of a zinc-only complex of an S100 protein to be determined. The zinc complex structure shows significant differences from those of both calcium-loaded and apo-S100A12 structures, and comparisons suggest an explanation for the zinc-induced 1500-fold increase in calcium affinity. In addition, the new structures provide insight into the role of zinc-calcium interplay in the transition of S100A12 from a dimer through a tetramer to a hexamer. The role of both zinc and calcium in target binding by S100A12 during host-parasite responses is confirmed by experiments with paramyosin from the tropical parasites Onchocerca volvulus and Brugia malayi. (C) 2009 Elsevier Ltd. All rights reserved.