PORCINE SUBMAXILLARY MUCIN AND HUMAN NORRIN

两个相关蛋白质的结构/功能关系将是 检查过了。猪颌下腺粘蛋白是一种糖蛋白，含有大约 67%的重量碳水化合物。粘蛋白可以润滑呼吸道， 胃肠道和泌尿生殖道，并保护上皮细胞免受 脱水和受伤。猪颌下腺粘蛋白结构的大部分 已经被阐明，但不是全部，包括单体粘蛋白是如何 分子聚集形成二聚体和多聚体粘蛋白，这些粘蛋白是 成熟的功能分子。形成中间的半胱氨酸- 二聚体和多聚体中的链内二硫键将是 下定决心。将对结构主题给予特别关注 CGLCG及其在多聚体粘蛋白组装中的作用这些研究将 利用定点突变和突变构建物的表达 在培养的动物细胞中。类似的研究将在以下方面进行 Norrin是一种在诺里病中有缺陷的133个残基的人类蛋白质， 一种X连锁的、隐性的人类神经疾病，特征是 失明、失聪和智力低下。这种蛋白质非常 在结构上类似于某些粘蛋白中形成二硫化物的结构域- 链接的倍增器。诺林中的半胱氨酸，形成中间和 链内二硫键的测定将使用相同的方法 还有颌下粘液。希望这些研究能揭示出 蛋白质中的富含二硫键的结构域导致低聚物 队形。

The structure/function relationships of two related proteins will be examined. Porcine submaxillary mucin is a glycoprotein containing about 67 percent by weight carbohydrate. Mucins lubricate the respiratory, gastrointestinal and urogenital tracts and protect epithelial cells from dehydration and injury. Much of porcine submaxillary mucin structure has been elucidated, but not all, including how the monomeric mucin molecules assemble to form dimeric and multimeric mucins that are the mature, functional molecules. The half-cystines that form the inter- and intrachain disulfide bonds in dimers and multimers will be determined. Particular attention will be given to the structural motif CGLCG and its role in assembly of multimeric mucin. These studies will utilize site-directed mutagenesis and expression of mutant constructs in animal cells in culture. Similar studies will be performed with norrin, a 133 residue human protein that is defective in Norrie disease, an X-linked, recessive human neurological disorder characterized by blindness, deafness and mental retardation. This protein is very similar structurally to the domain in some mucins that forms disulfide- linked multimers. The half-cystines in norrin that form inter- and intrachain disulfide bonds will be determined by the same methods used with submaxillary mucin. Hopefully, these studies will reveal how the disulfide-rich domains in proteins in which they occur lead to oligomer formation.