遗传 ›› 2010, Vol. 32 ›› Issue (11): 1126-1132.doi: 10.3724/SP.J.1005.2010.01126

• 综述 • 上一篇    下一篇

CDC/MACPF家族成孔毒素研究进展

乔旭, 吴芬芳, 苏鹏, 李庆伟   

  1. 辽宁师范大学海洋生物功能基因及蛋白质组学研究所, 大连 116029
  • 收稿日期:2010-05-04 修回日期:2010-07-13 出版日期:2010-11-20 发布日期:2010-11-25
  • 通讯作者: 李庆伟 E-mail:liqw@263.net
  • 基金资助:

    国家重点基础研究发展规划(973计划)项目(编号:2007CB815802), 国家高技术研究发展计划项目(863计划)(编号:2007AA09Z428)和国家教育部留学回国人员基金项目和辽宁省高校创新团队支持计划项目(编号:2006R32、2007T089 和2008T103)资助

Research progress on the MACPF/CDC family of pore-forming toxins

QIAO Xu, WU Fen-Fang, SU Peng, LI Qing-Wei   

  1. Institute of Marine Genomics & Proteomics, Liaoning Normal University, Dalian 116029, China
  • Received:2010-05-04 Revised:2010-07-13 Online:2010-11-20 Published:2010-11-25
  • Contact: LI Qing-Wei E-mail:liqw@263.net

摘要: 成孔毒素(Pore-forming toxins, PFTs)通常与细菌等原核生物的致病机理相关, 在真核生物中, 这类蛋白在免疫、胚胎发育、神经细胞迁移等方面发挥着重要作用。其中球状蛋白成孔毒素中的两大家族, 胆固醇结合细胞溶素(Cholesterol-dependent cytolysins, CDCs)和攻膜复合体/穿孔素超家族(Membrane attack complex/perforin superfamily, MACPF)以其独特的分子构型和功能受到研究者的关注。CDCs由革兰氏阳性细菌产生, 在细菌的侵染过程中发挥裂解靶细胞膜的作用; 在真核生物中, MACPF蛋白同时具有裂解和非裂解两种形式。目前, 对于以产气荚膜梭菌溶血素(PFO)为代表的CDCs蛋白的结构及分子机制了解得较为透彻, 近年来晶体学及生物化学研究揭示, 尽管CDCs和MACPF这两大家族成孔毒素在氨基酸序列水平上存在较大差异, 但它们共同的折叠模式预示: MACPF蛋白以一种类似于CDCs的成孔机制来行使其裂解靶膜的功能。文章对这两大家族成孔毒素的结构、成孔机制以及目前的研究热点问题予以综述, 为该领域今后的研究提供有益参考。

关键词: 成孔毒素, 胆固醇结合细胞溶素, 攻膜复合体/穿孔素超家族, 补体系统

Abstract: Pore-forming toxins (PFTs) are commonly associated with bacterial and other prokaryote pathogenesis. In eukaryotes, PFTs play important roles in immunity, embryonic development and neural-cell migration. Two families of globular protein PFTs: the cholesterol-dependent cytolysins (CDCs) and the membrane attack complex/perforin superfamily (MACPF), arrest researchers’ attention due to their unique molecular configuration and the function. CDCs are produced by Gram-positive bacteria and disrupt the membrane of host cells during infection. In eukaryotes, MACPF proteins have both lytic and non-lytic roles. With perfringolysin O (PFO) for example, the structure and molecular mechanism of CDCs are relatively well characterized. Recently crystallographic together with biochemical studies revealed that although MACPF and CDCs were extremely divergent at the amino acid sequence level, their common fold suggests that lytic MACPF proteins use a CDC-like mechanism of membrane disruption. This paper focuses on the structure, molecular mechanism of pore-formation and the research hotspot of the two families of PFTs, providing valuable clues for the future research in this field.

Key words: pore-forming toxins, cholesterol-dependent cytolysins, membrane attack complex/perforin superfamily, com-plement systerm