Shapiro L, Scherer P E
Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York 10029, USA.
Curr Biol. 1998 Mar 12;8(6):335-8. doi: 10.1016/s0960-9822(98)70133-2.
ACRP30--adipocyte complement-related protein of 30 kDa or AdipoQ--is an abundant serum protein, secreted exclusively from fat cells, which is implicated in energy homeostasis and obesity [1,2]. ACRP30 is a close homologue of the complement protein C1q, which is involved in the recognition of microbial surfaces [3-5] and antibody-antigen complexes [6,7] in the classical pathway of complement. We have determined the crystal structure of a homotrimeric fragment from ACRP30 at 2.1 A resolution. The structure reveals an unexpected homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and C1q families. We suggest that TNFs--which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis--arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between C1q-like proteins and TNFs illuminates the shared functions of these two important groups of proteins.
ACRP30——30 kDa的脂肪细胞补体相关蛋白或脂联素（AdipoQ）——是一种丰富的血清蛋白，仅由脂肪细胞分泌，与能量平衡和肥胖有关[1,2]。ACRP30是补体蛋白C1q的紧密同源物，C1q参与补体经典途径中微生物表面[3-5]和抗体-抗原复合物[6,7]的识别。我们已确定ACRP30一个同三聚体片段的晶体结构，分辨率为2.1埃。该结构揭示了与肿瘤坏死因子（TNF）家族意想不到的同源性。相同的折叠拓扑结构、关键残基保守性以及三聚体界面和内含子位置的相似性，牢固地确立了TNF家族与C1q家族之间的进化联系。我们认为，控制炎症、适应性免疫、细胞凋亡和能量平衡诸多方面的TNF，是由先天免疫系统的原始识别分子分化而来。C1q样蛋白与TNF之间的进化联系，阐明了这两组重要蛋白质的共同功能。
