X-ray structures of the microglia/macrophage-specific protein Iba1 from human and mouse demonstrate novel molecular conformation change induced by calcium binding
X-ray structures of the microglia/macrophage-specific protein Iba1 from human and mouse demonstrate novel molecular conformation change induced by calcium binding
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DOI：
10.1016/j.jmb.2006.09.027
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发表时间：
2006-12-01
影响因子：
5.6
通讯作者：
Kamitori, Shigehiro
中科院分区：
文献类型：
--
作者：
Yamada, Mitsugu;Ohsawa, Keiko;Kamitori, Shigehiro
Iba 1是一种钙离子结合蛋白，由147个氨基酸残基组成，在小胶质细胞/巨噬细胞中特异性表达，并被认为是激活小胶质细胞膜皱褶的关键因子。我们已经确定了晶体结构的人Iba 1的钙离子自由的形式和小鼠Iba 1的钙离子结合的形式，分辨率分别为1.9埃和2.1埃。Iba 1的X-射线结构揭示了一个紧凑的，单结构域的蛋白质与两个EF-手图案，显示出相似的整体拓扑结构的经典EF-手蛋白肌钙蛋白C和钙调蛋白的部分结构。在小鼠Iba 1中，第二EF-手含有结合的Ca 2+，但第一EF-手不，这通常是在S100蛋白中的情况，表明Iba 1具有S100蛋白样EF-手。Iba 1与Ca ~（2+）结合引起的分子构象变化与经典的EF-手蛋白和/或S100蛋白不同，表明Iba 1具有独特的依赖于Ca ~（2+）结合的分子转换机制，从而与靶分子相互作用。(c)2006爱思唯尔有限公司版权所有。
The ionized calcium-binding adaptor molecule 1 (Iba1) with 147 amino acid residues has been identified as a calcium-binding protein, expressed specifically in microglia/macrophages, and is expected to be a key factor in membrane ruffling, which is a typical feature of activated microglia. We have determined the crystal structure of human Iba1 in a Ca2+-free form and mouse Iba1 in a Ca2+-bound form, to a resolution of 1.9 angstrom and 2.1 angstrom, respectively. X-ray structures of Iba1 revealed a compact, single-domain protein with two EF-hand motifs, showing similarity in overall topology to partial structures of the classical EF-hand proteins troponin C and calmodulin. In mouse Iba1, the second EF-hand contains a bound Ca2+ but the first EF-hand does not, which is often the case in S100 proteins, suggesting that Iba1 has S100 protein-like EF-hands. The molecular conformational change induced by Ca2+-binding of Iba1 is different from that found in the classical EF-hand proteins and/or S100 proteins, which demonstrates that Iba1 has an unique molecular switching mechanism dependent on Ca2+-binding, to interact with target molecules. (c) 2006 Elsevier Ltd. All rights reserved.