Crystal structures of S100A6 in the Ca2+-free and Ca2+-bound states:: The calcium sensor mechanism of S100 proteins revealed at atomic resolution
Crystal structures of S100A6 in the Ca2+-free and Ca2+-bound states:: The calcium sensor mechanism of S100 proteins revealed at atomic resolution
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DOI：
10.1016/s0969-2126(02)00740-2
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发表时间：
2002-04-01
期刊：
影响因子：
5.7
通讯作者：
Dominguez, R
中科院分区：
文献类型：
--
作者：
Otterbein, LR;Kordowska, J;Dominguez, R
S100A6是Call结合蛋白S100家族的成员，由于其在各种肿瘤细胞中的过表达，其在癌症诊断中发挥重要作用。我们已经确定了人S100A6的晶体结构中的Ca2+自由和Ca2+结合状态的分辨率分别为1.15埃和1.44埃。Ca2+结合导致S100A6二聚体的整体形状和电荷分布发生显著变化，导致两个对称定位的靶结合位点暴露。结果与S100A6一致，并且很可能与其他S100蛋白一致，其以类似于原型传感器钙调蛋白和肌钙蛋白C的方式作为Ca2+传感器起作用。这些结构对于我们理解S100家族中Ca2+结合的靶结合和协同性具有重要意义。
S100A6 is a member of the S100 family of Call binding proteins, which have come to play an important role in the diagnosis of cancer due to their overexpression in various tumor cells. We have determined the crystal structures of human S100A6 in the Ca2+-free and Ca2+-bound states to resolutions of 1.15 Angstrom and 1.44 Angstrom, respectively. Ca2+ binding is responsible fora dramatic change in the global shape and charge distribution of the S100A6 dimer, leading to the exposure of two symmetrically positioned target binding sites. The results are consistent with S100A6, and most likely other S100 proteins, functioning as Ca2+ sensors in a way analogous to the prototypical sensors calmodulin and troponin C. The structures have important implications for our understanding of target binding and cooperativity of Ca2+ binding in the S100 family.