The structures of secretory and dimeric immunoglobulin A.
The structures of secretory and dimeric immunoglobulin A.
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DOI：
10.7554/elife.56098
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发表时间：
2020-10-27
期刊：
影响因子：
7.7
通讯作者：
Stadtmueller BM
中科院分区：
文献类型：
--
作者：
Kumar Bharathkar S;Parker BW;Malyutin AG;Haloi N;Huey-Tubman KE;Tajkhorshid E;Stadtmueller BM
Secretory (S) Immunoglobulin (Ig) A是主要的粘膜抗体，能结合病原体和共生微生物。SIgA是一种聚合抗体，通常含有两个IgA拷贝，它们与一条连接链（JC）结合形成二聚体(d) IgA，该二聚体与聚合igg受体外结构域结合，称为分泌成分（SC）。在此，我们报道了小鼠SIgA和dIgA的低温电镜结构。结构揭示了两个IgAs通过四个重链尾翼和JC连接在一起形成β-三明治状褶皱。两个IgAs相互弯曲和倾斜，形成不同的凹面和凸面。在SIgA中，SC被绑定到一个面，不对称地接触IgAs和JC。复杂组分的弯曲和倾斜排列限制了两组抗原结合片段（fab）的可能位置，并保留了受体结合位点的空间可及性，可能影响抗原结合和效应物的功能。
Secretory (S) Immunoglobulin (Ig) A is the predominant mucosal antibody, which binds pathogens and commensal microbes. SIgA is a polymeric antibody, typically containing two copies of IgA that assemble with one joining-chain (JC) to form dimeric (d) IgA that is bound by the polymeric Ig-receptor ectodomain, called secretory component (SC). Here, we report the cryo-electron microscopy structures of murine SIgA and dIgA. Structures reveal two IgAs conjoined through four heavy-chain tailpieces and the JC that together form a β-sandwich-like fold. The two IgAs are bent and tilted with respect to each other, forming distinct concave and convex surfaces. In SIgA, SC is bound to one face, asymmetrically contacting both IgAs and JC. The bent and tilted arrangement of complex components limits the possible positions of both sets of antigen-binding fragments (Fabs) and preserves steric accessibility to receptor-binding sites, likely influencing antigen binding and effector functions.