人甘露聚糖结合凝集素（MBL）上MBL相关丝氨酸蛋白酶结合基序的定位

Location of MBL-associated serine proteases binding motifs on human mannan-binding lectin (MBL).

作者信息

Zuo Daming, Cai Xuemin, Zhao Na, Zhang Liyun, Chen Zhengliang

机构信息

Department of Immunology, School of Basic Medical Sciences, Southern Medical University, 510515 Guangzhou, Guangdong, PR China.

出版信息

Protein Pept Lett. 2010 Jan;17(1):131-6. doi: 10.2174/092986610789909566.

DOI:10.2174/092986610789909566

PMID:20214636

Abstract

The lectin pathway provides an antibody independent route of complement activation. Mannan-binding lectin (MBL) can form compound with MBL-associated serine proteases (MASPs) through its collagen-like region (CLR) to initiate complement fixation. In this study, we designed and synthesized a range of peptides according to the sequence of CLR in human MBL, which were assumed to block the MBL-MASP interaction, in order to locate the serine protease binding motifs on human MBL. It was demonstrated that MASPs bind on the C-terminal side of the hinge region formed by an interruption in the Gly-X-Y repeat pattern of the collagen-like domain. In addition, Arg32Cys, Gly35Asp and Gly37Glu mutant proteins have the similar serine protease binding characteristic with wild type MBL, but the binding between mutated MBL proteins and MASPs is much weaker than that between wild type MBL protein and MASPs.

摘要

凝集素途径提供了一条不依赖抗体的补体激活途径。甘露聚糖结合凝集素（MBL）可通过其胶原样区域（CLR）与MBL相关丝氨酸蛋白酶（MASP）形成复合物，从而启动补体固定。在本研究中，我们根据人MBL中CLR的序列设计并合成了一系列肽段，推测这些肽段可阻断MBL与MASP的相互作用，以定位人MBL上的丝氨酸蛋白酶结合基序。结果表明，MASP结合在由胶原样结构域的Gly-X-Y重复模式中断形成的铰链区的C端一侧。此外，Arg32Cys、Gly35Asp和Gly37Glu突变蛋白与野生型MBL具有相似的丝氨酸蛋白酶结合特性，但突变的MBL蛋白与MASP之间的结合比野生型MBL蛋白与MASP之间的结合弱得多。