The structure of OMCI, a novel lipocalin inhibitor of the complement system

被引：46

作者：

Roversi, Pietro

Lissina, Olga

Johnson, Steven

Ahmat, Nurfilza

Paesen, Guido C.

Ploss, Kerstin

Boland, Wilhelm

Nunn, Miles A. ^{[1
]}

Lea, Susan M.

机构：

[1] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England

[2] NERC Ctr Environm Hydrol, Oxford OX1 3SR, England

[3] Max Planck Inst Chem Ecol, Dept Bioorgan Chem, D-00745 Jena, Germany

来源：

JOURNAL OF MOLECULAR BIOLOGY | 2007年 / 369卷 / 03期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金; 英国自然环境研究理事会; 英国医学研究理事会;

关键词：

omCI; tick; complement C5; complement inhibitor; lipocalin;

D O I：

10.1016/j.jmb.2007.03.064

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 complement (C) system is a potent innate immune defence system against parasites. We have recently characterised and expressed OmCI, a 16 kDa protein derived from the soft tick Ornithodoros moubata that specifically binds C5, thereby preventing C activation. The structure of recombinant OmCI determined at 1.9 angstrom resolution confirms a lipocalin fold and reveals that the protein binds a fatty acid derivative that we have identified by mass spectrometry as ricinoleic acid. We propose that OmCI could sequester one of the fatty acid-derived inflammatory modulators from the host plasma, thereby interfering with the host inflammatory response to the tick bite. Mapping of sequence differences between OmCI and other tick lipocalins with different functions, combined with biochemical investigations of OmCI activity, supports the hypothesis that OmCI acts by preventing interaction with the C5 convertase, rather than by blocking the C5a cleavage site. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：784 / 793

页数：10

共 61 条

[1] RETRACTED: The structure of complement C3b provides insights into complement activation and regulation (Retracted article. See vol. 532,2016) [J].