Crystal structure of Spot 14, a modulator of fatty acid synthesis.

Article Details


Colbert CL, Kim CW, Moon YA, Henry L, Palnitkar M, McKean WB, Fitzgerald K, Deisenhofer J, Horton JD, Kwon HJ

Crystal structure of Spot 14, a modulator of fatty acid synthesis.

Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18820-5. doi: 10.1073/pnas.1012736107. Epub 2010 Oct 15.

PubMed ID
20952656 [ View in PubMed

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 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.

DrugBank Data that Cites this Article

NameUniProt ID
Acetyl-CoA carboxylase 1Q13085Details
Acetyl-CoA carboxylase 2O00763Details