Drickamer K
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032.
Nature. 1992 Nov 12;360(6400):183-6. doi: 10.1038/360183a0.
Calcium-dependent or C-type carbohydrate-recognition domains are homologous protein modules found in a variety of animal lectins. Selective binding of sugars by these domains is essential for glycoprotein clearance, cell-cell adhesion and pathogen neutralization. Although various C-type carbohydrate-recognition domains share sequence identity ranging from 20 to 55%, their sugar-binding characteristics vary widely. The structure of a mannose-binding carbohydrate-recognition domain in complex with a saccharide ligand suggests that two glutamic acid-asparagine pairs are essential determinants of ligand binding by this domain. In C-type lectins that bind galactose with higher affinity than mannose, one of these pairs is replaced by glutamine-aspartic acid. Here we shift the sequence of the mannose-binding protein to correspond to that found in galactose-binding domains in order to test the importance of these residues in sugar-binding selectivity. This simple switch in the position of a single amide group alters the binding activity of the domain so that galactose becomes the preferred ligand.
钙依赖性或C型碳水化合物识别结构域是在多种动物凝集素中发现的同源蛋白质模块。这些结构域对糖的选择性结合对于糖蛋白清除、细胞间粘附和病原体中和至关重要。尽管各种C型碳水化合物识别结构域的序列同一性在20%至55%之间，但它们的糖结合特性差异很大。与糖类配体结合的甘露糖结合碳水化合物识别结构域的结构表明，两个谷氨酸-天冬酰胺对是该结构域结合配体的关键决定因素。在比甘露糖具有更高亲和力结合半乳糖的C型凝集素中，其中一对被谷氨酰胺-天冬氨酸取代。在这里，我们将甘露糖结合蛋白的序列改变为与半乳糖结合结构域中的序列一致，以测试这些残基在糖结合选择性中的重要性。单个酰胺基团位置的这种简单切换改变了该结构域的结合活性，使得半乳糖成为首选配体。
