The crystal structure of CHIR-AB1:: A primordial avian classical fc receptor
The crystal structure of CHIR-AB1:: A primordial avian classical fc receptor
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DOI：
10.1016/j.jmb.2008.06.082
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发表时间：
2008-09-12
影响因子：
5.6
通讯作者：
Bjorkman, Pamela J.
中科院分区：
文献类型：
--
作者：
Arnon, Tal I.;Kaiser, Jens T.;Bjorkman, Pamela J.
CHIR-AB 1是一种新发现的禽类免疫球蛋白（IG）受体，具有激活和抑制功能，因此被认为是一种潜在的双功能受体。最近，CHIR-AB 1被证明可以结合鸡IgY的Fc区，并通过与共同的γ链（一种在连接许多不同免疫受体时传递信号的亚基）结合来诱导钙动员。在这里，我们描述了CHIR-AB1的1.8埃分辨率晶体结构。胞外域T胞外域由单个C2型IG结构域组成，类似于哺乳动物Fc受体如Fc γ R和FcaRI中发现的Ig样结构域。与这些受体和其他单体IG超家族成员不同，CHIR-AB 1结晶为2倍对称同源二聚体，与抗体中的可变区或恒定区二聚体没有相似之处。超离心分析表明，CHIR-AB 1在溶液中以单体和二聚体的混合物形式存在，平衡凝胶过滤显示2：1的受体/配体结合化学计量比。1：1的CHIR-AB 1/IgY相互作用亲和力的测量表明相对低的亲和力复合物，但是2：1的CHIR-AB 1/IgY相互作用允许表观亲和力的增加，这是由于当受体被拴系到表面时的亲合力效应。总之，这些结果增加了对Fc受体及其功能机制的结构理解。(C)2008爱思唯尔有限公司保留所有权利。
CHIR-AB1 is a newly identified avian immunoglobulin (Ig) receptor that includes both activating and inhibitory motifs and was therefore classified as a potentially bifunctional receptor. Recently, CHIR-AB1 was shown to bind the Fc region of chicken IgY and to induce calcium mobilization via association with the common gamma-chain, a subunit that transmits signals upon ligation of many different immunoreceptors. Here we describe the 1.8-angstrom- resolution crystal structure of the CHIR-AB1. ectodomain. T ectodomain consists of a single C2-type Ig domain resembling the Ig-like domains found in mammalian Fc receptors such as Fc gamma Rs and FcaRI. Unlike these receptors and other monomeric Ig superfamily members, CHIR-AB1 crystallized as a 2-fold symmetrical homodimer that bears no resemblance to variable or constant region diners in an antibody. Analytical ultracentrifugation demonstrated that CHIR-AB1 exists as a mixture of monomers and dimers in solution, and equilibrium gel filtration revealed a 2:1 receptor/ligand binding stoichiometry. Measurement of the 1:1 CHIR-AB1/IgY interaction affinity indicates a relatively low affinity complex, but a 2:1 CHIR-AB1/IgY interaction allows an increase in apparent affinity due to avidity effects when the receptor is tethered to a surface. Taken together, these results add to the structural understanding of Fc receptors and their functional mechanisms. (C) 2008 Elsevier Ltd. All rights reserved.