1c28
THE CRYSTAL STRUCTURE OF A COMPLMENT-1Q FAMILY PROTEIN SUGGESTS AN EVOLUTIONARY LINK TO TUMOR NECROSIS FACTORTHE CRYSTAL STRUCTURE OF A COMPLMENT-1Q FAMILY PROTEIN SUGGESTS AN EVOLUTIONARY LINK TO TUMOR NECROSIS FACTOR
Structural highlights
Function[ADIPO_MOUSE] Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and activation in the liver and the skeletal muscle, enhancing glucose utilization and fatty-acid combustion. Antagonizes TNF-alpha by negatively regulating its expression in various tissues such as liver and macrophages, and also by counteracting its effects. Inhibits endothelial NF-kappa-B signaling through a cAMP-dependent pathway. May play a role in cell growth, angiogenesis and tissue remodeling by binding and sequestering various growth factors with distinct binding affinities, depending on the type of complex, LMW, MMW or HMW.[1] [2] [3] [4] [5] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedACRP30--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. The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor.,Shapiro L, Scherer PE Curr Biol. 1998 Mar 12;8(6):335-8. PMID:9512423[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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