The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor

Lawrence Shapiro, Philipp E. Scherer

Research output: Contribution to journalArticle

545 Scopus citations

Abstract

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 dose 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.

Original languageEnglish (US)
Pages (from-to)335-340
Number of pages6
JournalCurrent Biology
Volume8
Issue number6
DOIs
StatePublished - Mar 12 1998

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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