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

Christopher L. Colbert, Chai Wan Kim, Young Ah Moon, Lisa Henry, Maya Palnitkar, William B. McKean, Kevin Fitzgerald, Johann Deisenhofer, Jay D. Horton, Hyock Joo Kwon

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)18820-18825
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number44
DOIs
StatePublished - Nov 2 2010

Keywords

  • Lipogenesis
  • Posttranslational
  • Regulation

ASJC Scopus subject areas

  • General

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