Arlaud Gérard J, Gaboriaud Christine, Thielens Nicole M, Budayova-Spano Monika, Rossi Véronique, Fontecilla-Camps Juan Carlos
Laboratoire d'Enzymologie Moleculaire, Institut de Biologie Structurale Jean-Pierre Ebel, CEA-CNRS-Université Joseph Fourier, 41 Rue Jules Horowitz, Avenue des Martyrs, 38027 Grenoble Cedex 1, France.
Mol Immunol. 2002 Nov;39(7-8):383-94. doi: 10.1016/s0161-5890(02)00143-8.
C1 is the multimolecular protease that triggers activation of the classical pathway of complement, a major element of antimicrobial host defense also involved in immune tolerance and various pathologies. This 790,000 Da complex is formed from the association of a recognition protein, C1q, and a catalytic subunit, the Ca2+-dependent tetramer C1s-C1r-C1r-C1s comprising two copies of each of the modular proteases C1r and C1s. Early studies mainly based on biochemical analysis and electron microscopy of C1 and its isolated components have allowed for characterization of their domain structure and led to a low-resolution model of the C1 complex in which the elongated C1s-C1r-C1r-C1s tetramer folds into a more compact, "8-shaped" conformation upon interaction with C1q. A major strategy used over the past years has been to dissect the C1 proteins into modular segments to characterize their function and solve their structure by either X-ray crystallography or nuclear magnetic resonance spectroscopy (NMR). The purpose of this review is to focus on this information, with particular emphasis on the architecture of the C1 complex and the mechanisms underlying its activation and proteolytic activity.
C1是一种多分子蛋白酶，可触发补体经典途径的激活，补体经典途径是抗菌宿主防御的主要组成部分，也参与免疫耐受和各种病理过程。这个790,000道尔顿的复合物由一种识别蛋白C1q和一个催化亚基组成，即Ca2+依赖性四聚体C1s-C1r-C1r-C1s，其中包含模块化蛋白酶C1r和C1s各两份。早期研究主要基于对C1及其分离成分的生化分析和电子显微镜观察，得以对其结构域结构进行表征，并得出了C1复合物的低分辨率模型，其中细长的C1s-C1r-C1r-C1s四聚体在与C1q相互作用时折叠成更紧凑的“8字形”构象。过去几年使用的主要策略是将C1蛋白分解为模块化片段，以通过X射线晶体学或核磁共振光谱（NMR）表征其功能并解析其结构。本综述的目的是聚焦于这些信息，特别强调C1复合物的结构以及其激活和蛋白水解活性的潜在机制。
