Fredslund Folmer, Laursen Nick S, Roversi Pietro, Jenner Lasse, Oliveira Cristiano L P, Pedersen Jan S, Nunn Miles A, Lea Susan M, Discipio Richard, Sottrup-Jensen Lars, Andersen Gregers R
Department of Molecular Biology, University of Aarhus, DK-8000 Aarhus, Denmark.
Nat Immunol. 2008 Jul;9(7):753-60. doi: 10.1038/ni.1625. Epub 2008 Jun 8.
To provide insight into the structural and functional properties of human complement component 5 (C5), we determined its crystal structure at a resolution of 3.1 A. The core of C5 adopted a structure resembling that of C3, with the domain arrangement at the position corresponding to the C3 thioester being very well conserved. However, in contrast to C3, the convertase cleavage site in C5 was ordered and the C345C domain flexibly attached to the core of C5. Binding of the tick C5 inhibitor OmCI to C5 resulted in stabilization of the global conformation of C5 but did not block the convertase cleavage site. The structure of C5 may render possible a structure-based approach for the design of new selective complement inhibitors.
为深入了解人补体成分5（C5）的结构和功能特性，我们测定了其分辨率为3.1埃的晶体结构。C5的核心采用了类似于C3的结构，在与C3硫酯相对应的位置上的结构域排列非常保守。然而，与C3不同的是，C5中的转化酶切割位点是有序的，并且C345C结构域灵活地连接到C5的核心。蜱C5抑制剂OmCI与C5的结合导致C5整体构象的稳定，但并未阻断转化酶切割位点。C5的结构可能为设计新型选择性补体抑制剂提供基于结构的方法。
