Department of Biochemistry and Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9050, USA.
Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18820-5. doi: 10.1073/pnas.1012736107. Epub 2010 Oct 15.
Spot 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 Å 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.
S14 是一种在产脂组织中大量表达的蛋白质，其调控方式类似于参与脂肪酸合成的其他酶。在泌乳期乳腺组织中敲除 S14 会减少脂质合成，但 S14 作用的机制尚不清楚。我们在此呈现 S14 的晶体结构至 2.65Å，以及生化数据表明 S14 可以与 MIG12 形成异二聚体。MIG12 通过诱导乙酰辅酶 A 羧化酶的聚合和活性，即脂肪酸合成途径中的第一个关键酶反应，来调节脂肪酸合成。S14 和 MIG12 的共表达导致异二聚体形成，乙酰辅酶 A 羧化酶的聚合和活性降低。S14 的结构提示了一种机制，即与 MIG12 形成异二聚体减弱了 MIG12 激活 ACC 的能力。
