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The Crystal Structure of Spot14, a modulator of lipogenesisThe Crystal Structure of Spot14, a modulator of lipogenesis
Structural highlights
FunctionTHRSP_MOUSE Plays a role in the regulation of lipogenesis, especially in lactating mammary gland. Important for the biosynthesis of triglycerides with medium-length fatty acid chains. May modulate lipogenesis by interacting with MID1IP1 and preventing its interaction with ACACA. May function as transcriptional coactivator. May modulate the transcription factor activity of THRB (By similarity).[1] [2] Publication Abstract from PubMedSpot 14 (S14) is a protein that is abundantly expressed in lipogenic tissues and is regulated in a manner similar to other enzymes involved in fatty acid synthesis. Deletion of S14 in mice decreased lipid synthesis in lactating mammary tissue, but the mechanism of S14's action is unknown. Here we present the crystal structure of S14 to 2.65 A and biochemical data showing that S14 can form heterodimers with MIG12. MIG12 modulates fatty acid synthesis by inducing the polymerization and activity of acetyl-CoA carboxylase, the first committed enzymatic reaction in the fatty acid synthesis pathway. Coexpression of S14 and MIG12 leads to heterodimers and reduced acetyl-CoA carboxylase polymerization and activity. The structure of S14 suggests a mechanism whereby heterodimer formation with MIG12 attenuates the ability of MIG12 to activate ACC. Crystal structure of Spot 14, a modulator of fatty acid synthesis.,Colbert CL, Kim CW, Moon YA, Henry L, Palnitkar M, McKean WB, Fitzgerald K, Deisenhofer J, Horton JD, Kwon HJ Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18820-5. Epub 2010 Oct 15. PMID:20952656[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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