Bonner Alexandra, Perrier Clémentine, Corthésy Blaise, Perkins Stephen J
Department of Biochemistry and Molecular Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, United Kingdom.
J Biol Chem. 2007 Jun 8;282(23):16969-80. doi: 10.1074/jbc.M701281200. Epub 2007 Apr 11.
Secretory component (SC) in association with polymeric IgA (pIgA) forms secretory IgA, the major antibody active at mucosal surfaces. SC also exists in the free form, with innate-like neutralizing properties against pathogens. Free SC consists of five glycosylated variable (V)-type Ig domains (D1-D5), whose structure was determined by x-ray and neutron scattering, ultracentrifugation, and modeling. With a radius of gyration of 3.53-3.63 nm, a length of 12.5 nm, and a sedimentation coefficient of 4.0 S, SC possesses an unexpected compact structure. Constrained scattering modeling based on up to 13,000 trial models shows that SC adopts a J-shaped structure in which D4 and D5 are folded back against D2 and D3. The seven glycosylation sites are located on one side of SC, leaving known IgA-binding motifs free to interact with pIgA. This work represents the first analysis of the three-dimensional structure of full-length free SC and paves the way to a better understanding of the association between SC and its potential ligands, i.e. pIgA and pathogenic-associated motifs.
分泌成分（SC）与聚合免疫球蛋白A（pIgA）结合形成分泌型免疫球蛋白A，这是在黏膜表面起主要作用的抗体。SC也以游离形式存在，对病原体具有类似天然免疫的中和特性。游离SC由五个糖基化的可变（V）型免疫球蛋白结构域（D1-D5）组成，其结构通过X射线和中子散射、超速离心及建模得以确定。SC的回转半径为3.53-3.63纳米，长度为12.5纳米，沉降系数为4.0 S，具有意想不到的紧密结构。基于多达13000个试验模型的受限散射建模表明，SC呈现J形结构，其中D4和D5折叠回与D2和D3相对的位置。七个糖基化位点位于SC的一侧，使已知的免疫球蛋白A结合基序能够自由地与pIgA相互作用。这项工作代表了对全长游离SC三维结构的首次分析，为更好地理解SC与其潜在配体（即pIgA和致病相关基序）之间的关联铺平了道路。
