Bonner A, Almogren A, Furtado P B, Kerr M A, Perkins S J
Division of Biosciences, Institute of Structural and Molecular Biology, University College London, London, UK.
Mucosal Immunol. 2009 Jan;2(1):74-84. doi: 10.1038/mi.2008.68. Epub 2008 Oct 8.
Secretory immunoglobulin A (SIgA) is the most prevalent antibody in the human body and a first line of defense in mucosal immunity. We located secretory component (SC) relative to dimeric IgA1 (dIgA1) within the SIgA1 structure using the constrained modeling of solution scattering and analytical ultracentrifugation data. The extended solution structure of dIgA1 is largely preserved within SIgA1. From conformational searches of SC locations, the best-fit SC models within SIgA1 show that SC is extended along the outermost convex edge of the Fc dimer in dIgA1. The topology of our SIgA1 structure reveals that it is able to bind to one FcalphaRI receptor molecule. SC binding to the Fc dimer confers protection to SIgA1 by the masking of proteolytically susceptible surface sites from bacterial proteases in the harsh environment of the mucosa. The models support a "zipper-like" unfolding of SC upon dIgA1 in the formation and transportation of SIgA1 into the mucosa.
分泌型免疫球蛋白A（SIgA）是人体中最普遍的抗体，也是黏膜免疫的第一道防线。我们利用溶液散射和分析超速离心数据的约束建模，在SIgA1结构中确定了分泌成分（SC）相对于二聚体IgA1（dIgA1）的位置。dIgA1的扩展溶液结构在SIgA1中基本保持不变。通过对SC位置的构象搜索，SIgA1中最佳拟合的SC模型表明，SC沿着dIgA1中Fc二聚体的最外凸边缘延伸。我们的SIgA1结构拓扑显示它能够结合一个FcalphaRI受体分子。SC与Fc二聚体的结合通过在黏膜恶劣环境中屏蔽细菌蛋白酶易水解的表面位点，为SIgA1提供保护。这些模型支持在SIgA1形成并转运到黏膜过程中，dIgA1上的SC呈“拉链状”展开。
