Interaction of Mannose-binding Protein with Associated Serine Proteases
Interaction of Mannose-binding Protein with Associated Serine Proteases
复制标题
甘露糖结合蛋白与相关丝氨酸蛋白酶的相互作用
DOI：
10.1074/jbc.m004030200
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
R. Dodd
中科院分区：
文献类型：
--
作者：
R. Wallis;R. Dodd
甘露糖结合蛋白（MBP;甘露糖结合凝集素）形成先天免疫系统的一部分。通过直接结合到潜在微生物病原体表面上的碳水化合物，MBP和MBP相关丝氨酸蛋白酶（MASP）可以取代经典补体途径的抗体和补体成分C1 q，C1 r和C1 s。为了研究MBP激活MASP的机制，分离了大鼠MASP-1和-2的cDNA，并表达和纯化了包含N-末端CUB和表皮生长因子样结构域的部分。纯化的蛋白质的生物物理表征表明，每个截短的MASP在溶液中是Ca 2+非依赖性同源二聚体，其中相互作用模块包括N-末端两个结构域。结合研究表明，这两个MASPs关联独立与大鼠MBP在Ca 2+依赖性的方式，通过相互作用，涉及N-末端的三个结构域。截短的MASPs的生物物理性质表明，与MBP的相互作用，导致补体激活显着不同的经典途径的组件C1 q，C1 r和C1 s之间的。通过含有与人免疫缺陷相关的那些等同的天然存在的突变的大鼠MBP对MASP结合的分析表明，与截短的MASP-1和MASP-2蛋白的结合在此类突变体中是有缺陷的。
Mannose-binding protein (MBP; mannose-binding lectin) forms part of the innate immune system. By binding directly to carbohydrates on the surfaces of potential microbial pathogens, MBP and MBP-associated serine proteases (MASPs) can replace antibodies and complement components C1q, C1r, and C1s of the classical complement pathway. In order to investigate the mechanisms of MASP activation by MBP, the cDNAs of rat MASP-1 and -2 have been isolated, and portions encompassing the N-terminal CUB and epidermal growth factor-like domains have been expressed and purified. Biophysical characterization of the purified proteins indicates that each truncated MASP is a Ca2+-independent homodimer in solution, in which the interacting modules include the N-terminal two domains. Binding studies reveal that both MASPs associate independently with rat MBP in a Ca2+-dependent manner through interactions involving the N-terminal three domains. The biophysical properties of the truncated MASPs indicate that the interactions with MBP leading to complement activation differ significantly from those between components C1q, C1r, and C1s of the classical pathway. Analysis of MASP binding by rat MBP containing naturally occurring mutations equivalent to those associated with human immunodeficiency indicates that binding to both truncated MASP-1 and MASP-2 proteins is defective in such mutants.
DOI：
10.1016/s0021-9258(18)61070-1
发表时间：
1987-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
P. Matsudaira
通讯作者：
P. Matsudaira