Bakos M A, Kurosky A, Goldblum R M
Department of Pediatrics, University of Texas Medical Branch, Galveston 77550.
J Immunol. 1991 Nov 15;147(10):3419-26.
Secretory component (SC) is an integral membrane glycoprotein of secretory epithelial cells which is responsible for the specific transport of polymeric Ig (PIg) to external mucosal surfaces. The ectoplasmic segment which binds polymeric Ig is comprised of five Ig-type domains. Chemically and enzymatically modified forms of the ectoplasmic portion of SC (FSC) were produced and tested for their ability to bind to PIgA and PIgM. Deglycosylated FSC bound specifically to PIg, indicating that N-linked carbohydrate moieties on FSC are not required for binding. Denatured, reduced, and alkylated FSC did not bind to PIgA, and bound to PIgM with significantly reduced affinity, suggesting that native conformation of the polypeptide backbone of SC was important to binding. Tryptic fragments of FSC which bound to PIg were isolated and identified to be derived from domain I of SC. Synthetic peptides comprising overlapping portions of domain I bound to PIg to varying degrees. The strongest affinity was demonstrated by a peptide comprised of residues 15 to 37 of SC. A comparison of the amino acid sequences of human, rabbit, and rat SC indicated that this region contained a high degree of residue identity (78%) and may represent a consensus sequence for binding of FSC to PIg. Importantly, the peptide comprised of residues 15 to 37 was also recognized by a monoclonal antibody, 6G11, which inhibited the binding of FSC to PIgA. These results demonstrate that the binding of human SC to PIg is critically dependent on a highly conserved peptide region within the first domain of SC centering at residues 15-37.
分泌成分（SC）是分泌上皮细胞的一种整合膜糖蛋白，负责将聚合免疫球蛋白（PIg）特异性转运至外部黏膜表面。结合聚合免疫球蛋白的胞外段由五个免疫球蛋白（Ig）类型的结构域组成。制备了分泌成分胞外部分（FSC）的化学修饰和酶促修饰形式，并测试它们结合多聚免疫球蛋白A（PIgA）和多聚免疫球蛋白M（PIgM）的能力。去糖基化的FSC特异性结合PIg，表明FSC上的N-连接碳水化合物部分对结合并非必需。变性、还原和烷基化的FSC不与PIgA结合，与PIgM的结合亲和力显著降低，这表明SC多肽主链的天然构象对结合很重要。分离出与PIg结合的FSC胰蛋白酶片段，并鉴定其来源于SC的结构域I。包含结构域I重叠部分的合成肽与PIg有不同程度的结合。由SC的15至37位残基组成的肽表现出最强的亲和力。对人、兔和大鼠SC的氨基酸序列比较表明，该区域具有高度的残基同一性（78%），可能代表FSC与PIg结合的共有序列。重要的是，由15至37位残基组成的肽也被单克隆抗体6G11识别，该抗体可抑制FSC与PIgA的结合。这些结果表明，人SC与PIg的结合关键取决于SC第一个结构域内以15 - 37位残基为中心的高度保守肽段区域。
