Flexibility in Mannan-Binding Lectin-Associated Serine Proteases-1 and-2 Provides Insight on Lectin Pathway Activation

被引：11

作者：

Nan, Ruodan ^{[1
]}

Furze, Christopher M. ^{[2
,3
]}

Wright, David W. ^{[1
]}

Gor, Jayesh ^{[1
]}

Wallis, Russell ^{[2
,3
]}

Perkins, Stephen J. ^{[1
]}

机构：

[1] UCL, Div Biosci, Dept Struct & Mol Biol, Darwin Bldg,Gower St, London WC1E 6BT, England

[2] Univ Leicester, Dept Infect Immun & Inflammat, Univ Rd, Leicester LE1 9HN, Leics, England

[3] Univ Leicester, Dept Mol Cell Biol, Univ Rd, Leicester LE1 9HN, Leics, England

来源：

STRUCTURE | 2017年 / 25卷 / 02期

基金：

英国工程与自然科学研究理事会;

关键词：

NATURALLY-OCCURRING MUTATIONS; X-RAY-STRUCTURE; COMPLEMENT ACTIVATION; STRUCTURAL BASIS; CLASSICAL PATHWAY; CRYSTAL-STRUCTURE; MASP-1; PROTEIN; RECOGNITION; COMPLEXES;

D O I：

10.1016/j.str.2016.12.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The lectin pathway of complement is activated by complexes comprising a recognition component (mannose-binding lectin, serum ficolins, collectin-LK or collectin-K1) and a serine protease (MASP-1 or MASP-2). MASP-1 activates MASP-2, and MASP-2 cleaves C4 and C4b-bound C2. To clarify activation, new crystal structures of Ca2+-bound MASP dimers were determined, together with their solution structures from X-ray scattering, analytical ultracentrifugation, and atomistic modeling. Solution structures of the CUB1-EGF-CUB2 dimer of each MASP indicate that the two CUB2 domains were tilted by as much as 90 degrees compared with the crystal structures, indicating considerable flexibility at the EGF-CUB2 junction. Solution structures of the full-length MASP dimers in their zymogen and activated forms revealed similar structures that were much more bent than anticipated from crystal structures. We conclude that MASP-1 and MASP-2 are flexible at multiple sites and that this flexibility may permit both intra-and inter-complex activation.

引用

页码：364 / 375

页数：12