Crystal structure of human complement protein C8gamma at 1.2 A resolution reveals a lipocalin fold and a distinct ligand binding site.
Crystal structure of human complement protein C8gamma at 1.2 A resolution reveals a lipocalin fold and a distinct ligand binding site.
复制标题
人补体蛋白 C8gamma 的晶体结构在 1.2 A 分辨率下显示出脂质运载蛋白折叠和独特的配体结合位点。
DOI：
10.1021/bi025696i
复制
发表时间：
2002
期刊：
影响因子：
2.9
通讯作者：
Lebioda,Lukasz
中科院分区：
文献类型：
--
作者：
Ortlund,Eric;Parker,ChastaL;Schreck,StevenF;Ginell,Steve;Minor,Wladek;Sodetz,JamesM;Lebioda,Lukasz
C8γ是人C8的22 kDa亚基，是补体的溶细胞膜攻击复合物（MAC）的五种组分之一。C8γ与C8α亚基以二硫键连接，C8α亚基与C8β链非共价结合。本研究中，重组C8γ的三维结构通过X-射线衍射测定，分辨率为1.2 μ m。该结构显示典型的脂质运载蛋白折叠，形成具有不同结合口袋的萼，这表明C8γ的配体结合功能。与其他脂质运载蛋白相比，其整体结构与中性粒细胞明胶酶相关脂质运载蛋白（NGAL）最相似，NGAL是一种从活化的中性粒细胞颗粒释放的蛋白质。值得注意的差异包括C8γ中更深的结合口袋以及口袋内衬残基的身份和位置的变化。在C8γ中，这些残基允许配体进入位于花萼基部的大疏水空腔，而NGAL中的相应残基限制进入。这表明C8γ和NGAL的天然配体在大小上显著不同。C8γ中的Cys 40与C8α形成二硫键，位于靠近花萼开口的部分无序环（环1，残基38−52）中。在MAC形成过程中，对C8α构象变化的反应，可以通过该环的运动来调节对花萼的进入。
C8γ is a 22-kDa subunit of human C8, which is one of five components of the cytolytic membrane attack complex of complement (MAC). C8γ is disulfide-linked to a C8α subunit that is noncovalently associated with a C8β chain. In the present study, the three-dimensional structure of recombinant C8γ was determined by X-ray diffraction to 1.2 Å resolution. The structure displays a typical lipocalin fold forming a calyx with a distinct binding pocket that is indicative of a ligand-binding function for C8γ. When compared to other lipocalins, the overall structure is most similar to neutrophil gelatinase associated lipocalin (NGAL), a protein released from granules of activated neutrophils. Notable differences include a much deeper binding pocket in C8γ as well as variation in the identity and position of residues lining the pocket. In C8γ, these residues allow ligand access to a large hydrophobic cavity at the base of the calyx, whereas corresponding residues in NGAL restrict access. This suggests the natural ligands for C8γ and NGAL are significantly different in size. Cys40in C8γ, which forms the disulfide bond to C8α, is located in a partially disordered loop (loop 1, residues 38−52) near the opening of the calyx. Access to the calyx may be regulated by movement of this loop in response to conformational changes in C8α during MAC formation.