Cell membranes and liposomes dissociate C-reactive protein (CRP) to form a new, biologically active structural intermediate:: mCRPm

被引:171
作者
Ji, Shang-Rong
Wu, Yi
Zhu, Li
Potempa, Lawrence A.
Sheng, Fen-Ling
Lu, Wei
Zhao, Jing
机构
[1] Lanzhou Univ, Inst Biophys, MOE Key Lab Arid & Grassland Ecol, Lanzhou 730000, Peoples R China
[2] Lanzhou Univ, Inst Cell Biol, Lanzhou 730000, Peoples R China
[3] Lanzhou Univ, Instrumental Anal Res Ctr, Lanzhou 730000, Peoples R China
[4] Immtech Pharmaceut Inc, Vernon Hills, IL USA
关键词
inflammation; cardiovascular disease; protein-membrane interaction;
D O I
10.1096/fj.06-6722com
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
Emerging evidence indicates that C-reactive protein (CRP) has at least two conformationally distinct isoforms, i.e., pentameric CRP (pCRP) and monomeric CRP (mCRP or CRP subunit). Both CRP isoforms are proposed to play roles in inflammation and may participate in the pathogenesis of cardiovascular disease. However, the origin of mCRP in situ and the interplay between the two CRP isoforms under physiological/ pathological circumstances remain elusive. Herein, by probing conformational alteration, neoepitope expression, and direct visualization using electron-microscopy, we have shown that calcium-dependent binding of pCRP to membranes, including liposomes and cell membranes, led to a rapid but partial structural change, producing molecules that express CRP subunit antigenicity but with retained native pentameric conformation. This hybrid molecule is herein termed mCRP(m). The formation of mCRPm was associated with significantly enhanced complement fixation. mCRP(m) can further detach from membrane to form the well-recognized mCRP isoform converted in solution (mCRP(s)) and exert potent stimulatory effects on endothelial cells. The membrane-induced pCRP dissociation not only provides a physiologically relevant scenario for mCRP formation but may represent an important mechanism for regulating CRP function.
引用
收藏
页码:284 / 294
页数:11
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