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From Proteopedia
Crystal structure of CIDE-N domain of FSP27
Structural highlights
FunctionCIDEC_MOUSE Binds to lipid droplets and regulates their enlargement, thereby restricting lipolysis and favoring storage. At focal contact sites between lipid droplets, promotes directional net neutral lipid transfer from the smaller to larger lipid droplets. The transfer direction may be driven by the internal pressure difference between the contacting lipid droplet pair. Its role in neutral lipid transfer and lipid droplet enlargement is activated by the interaction with PLIN1. May act as a CEBPB coactivator in the white adipose tissue to control the expression of a subset of CEBPB downstream target genes, including SOCS1, SOCS3, TGFB1, TGFBR1, ID2 and XDH. When overexpressed in preadipocytes, induces apoptosis or increases cell susceptibility to apoptosis induced by serum deprivation or TGFB treatment. As mature adipocytes, that express high CIDEC levels, are quite resistant to apoptotic stimuli, the physiological significance of its role in apoptosis is unclear. May play a role in the modulation of the response to osmotic stress by preventing NFAT5 to translocate into the nucleus and activate its target genes expression.[1] [2] [3] [4] Publication Abstract from PubMedFSP27 (CIDE-3 in humans) plays critical roles in lipid metabolism and apoptosis and is known to be involved in regulation of lipid droplet (LD) size and lipid storage and apoptotic DNA fragmentation. Given that CIDE-containing proteins including FSP27 are associated with many human diseases including cancer, aging, diabetes, and obesity, studies of FSP27 and other CIDE-containing proteins are of great biological importance. As a first step toward elucidating the molecular mechanisms of FSP27-mediated lipid droplet growth and apoptosis, we report the crystal structure of the CIDE-N domain of FSP27 at a resolution of 2.0 A. The structure revealed a possible biologically important homo-dimeric interface similar to that formed by the hetero-dimeric complex, CAD/ICAD. Comparison with other structural homologues revealed that the PB1 domain of BEM1P, ubiquitin-like domain of BAG6 and ubiquitin are structurally similar proteins. Our homo-dimeric structure of the CIDE-N domain of FSP27 will provide important information that will enable better understanding of the function of FSP27. Molecular basis for homo-dimerization of the CIDE domain revealed by the crystal structure of the CIDE-N domain of FSP27.,Lee SM, Jang TH, Park HH Biochem Biophys Res Commun. 2013 Oct 4;439(4):564-9. doi:, 10.1016/j.bbrc.2013.09.018. Epub 2013 Sep 8. PMID:24025675[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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