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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetyl-CoA Carboxylase / genetics
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Acetyl-CoA Carboxylase / metabolism
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Animals
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CHO Cells
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Cricetinae
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Cricetulus
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Crystallography, X-Ray
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Fatty Acids / biosynthesis*
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Fatty Acids / chemistry
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Fatty Acids / genetics
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Female
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Mice
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Microtubule-Associated Proteins / chemistry*
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism*
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Models, Molecular*
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Nuclear Proteins / chemistry*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Protein Structure, Tertiary
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Structure-Activity Relationship
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Transcription Factors / chemistry*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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Fatty Acids
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Microtubule-Associated Proteins
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Mig12 protein, mouse
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Nuclear Proteins
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Thrsp protein, mouse
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Transcription Factors
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Acetyl-CoA Carboxylase