Structural requirements for the interaction of human IgM and IgA with the human Fcalpha/mu receptor.
Structural requirements for the interaction of human IgM and IgA with the human Fcalpha/mu receptor.
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DOI：
10.1002/eji.200839184
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发表时间：
2009-04
影响因子：
5.4
通讯作者：
Pleass, Richard J.
中科院分区：
文献类型：
--
作者：
Ghumra, Ashfaq;Shi, Jianguo;Mcintosh, Richard S.;Rasmussen, Ingunn B.;Braathen, Ranveig;Johansen, Finn-Eirik;Sandlie, Inger;Mongini, Patricia K.;Areschoug, Thomas;Lindahl, Gunnar;Lewis, Melanie J.;Woof, Jenny M.;Pleass, Richard J.
在这里，我们揭示了人免疫球蛋白M和免疫球蛋白A的结构特征，这些结构特征决定了它们与人Fcα/μ受体(α/μR)的相互作用。配体聚合状态对相互作用是至关重要的，因为α/μR不与任何一类单体抗体发生结合。HFCα/μR与Ig M结合的亲和力在纳摩尔范围内，而与二聚体Ig A(DIGA)的亲和力则低10倍。用突变型Ig M和DIGA面板鉴定与hFCα/μR结合的关键区域。IGM结合需要Cμ3和Cμ4 Fc结构域的贡献，而对于DIGA来说，Cα3结构域中暴露的环是至关重要的。这个由Pro440-Phe443残基组成的环位于Fc结构域的界面上，参与了宿主受体FcαRI和聚合免疫球蛋白受体的结合，以及某些病原菌产生的免疫球蛋白结合蛋白。Pro440-Phe443环内的替换导致hfcα/μR结合的丢失。此外，分泌成分(SC，pIg R的胞外部分)和细菌Ig A结合蛋白显示抑制DIGA-hFcα/μR的相互作用。因此，我们在Ig A-Fc结构域间区域确定了一个对Hfcα/μR相互作用至关重要的基序，并强调了在Ig A Fc结构域界面上蛋白质-蛋白质相互作用的关键位点的多功能性质。
Here we unravel the structural features of human IgM and IgA that govern their interaction with the human Fcα/μ receptor (hFcα/μR). Ligand polymerization status was crucial for the interaction, because hFcα/μR binding did not occur with monomeric Ab of either class. hFcα/μR bound IgM with an affinity in the nanomolar range, whereas the affinity for dimeric IgA (dIgA) was tenfold lower. Panels of mutant IgM and dIgA were used to identify regions critical for hFcα/μR binding. IgM binding required contributions from both Cμ3 and Cμ4 Fc domains, whereas for dIgA, an exposed loop in the Cα3 domain was crucial. This loop, comprising residues Pro440–Phe443, lies at the Fc domain interface and has been implicated in the binding of host receptors FcαRI and polymeric Ig receptor (pIgR), as well as IgA-binding proteins produced by certain pathogenic bacteria. Substitutions within the Pro440–Phe443 loop resulted in loss of hFcα/μR binding. Furthermore, secretory component (SC, the extracellular portion of pIgR) and bacterial IgA-binding proteins were shown to inhibit the dIgA–hFcα/μR interaction. Therefore, we have identified a motif in the IgA–Fc inter-domain region critical for hFcα/μR interaction, and highlighted the multi-functional nature of a key site for protein–protein interaction at the IgA Fc domain interface.
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影响因子：
15.3
作者：
Carayannopoulos, L;Hexham, JM;Capra, JD
通讯作者：
Capra, JD
影响因子：
64.8
作者：
DUNCAN, AR;WOOF, JM;WINTER, G
通讯作者：
WINTER, G
影响因子：
56.9
作者：
DeLano, WL;Ultsch, MH;Wells, JA
通讯作者：
Wells, JA
DOI：
10.1074/jbc.m709844200
发表时间：
2008-06-20
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Lewis MJ;Meehan M;Owen P;Woof JM
通讯作者：
Woof JM
影响因子：
4.4
作者：
Ober, RJ;Radu, CG;Ward, ES
通讯作者：
Ward, ES