TY - JOUR
T1 - The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor
AU - Shapiro, Lawrence
AU - Scherer, Philipp E.
N1 - Funding Information:
We thank C.M. Ogata and W.A. Hendrickson for help with data collection at beam-line X4A, M. Lisanti for help in the earliest stages of this work, and D.H. Fremont, Y. Choi, A.K. Aggarwal and P.D. Kwong for helpful comments. Beam-line X4A at the National Syncrotron Light Source at Brookhaven National Lab, a DOE facility, is supported by the Howard Hughes Medical Institute. Coordinates have been deposited in the Brookhaven Protein Data Bank.
PY - 1998/3/12
Y1 - 1998/3/12
N2 - 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.
AB - 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.
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U2 - 10.1016/s0960-9822(98)70133-2
DO - 10.1016/s0960-9822(98)70133-2
M3 - Article
C2 - 9512423
AN - SCOPUS:0032510463
SN - 0960-9822
VL - 8
SP - 335
EP - 340
JO - Current Biology
JF - Current Biology
IS - 6
ER -