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 journalArticle

35 Citations (Scopus)

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

Fingerprint

Acetyl-CoA Carboxylase
Fatty Acids
Polymerization
Breast
Lipids
Enzymes
Proteins

Keywords

  • Lipogenesis
  • Posttranslational
  • Regulation

ASJC Scopus subject areas

  • General

Cite this

Crystal structure of Spot 14, a modulator of fatty acid synthesis. / Colbert, Christopher L.; Kim, Chai Wan; Moon, Young Ah; Henry, Lisa; Palnitkar, Maya; McKean, William B.; Fitzgerald, Kevin; Deisenhofer, Johann; Horton, Jay D.; Kwon, Hyock Joo.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 44, 02.11.2010, p. 18820-18825.

Research output: Contribution to journalArticle

Colbert, Christopher L. ; Kim, Chai Wan ; Moon, Young Ah ; Henry, Lisa ; Palnitkar, Maya ; McKean, William B. ; Fitzgerald, Kevin ; Deisenhofer, Johann ; Horton, Jay D. ; Kwon, Hyock Joo. / Crystal structure of Spot 14, a modulator of fatty acid synthesis. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 44. pp. 18820-18825.
@article{033be659c6cf4a23a42042464517db3c,
title = "Crystal structure of Spot 14, a modulator of fatty acid synthesis",
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 {\AA} 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.",
keywords = "Lipogenesis, Posttranslational, Regulation",
author = "Colbert, {Christopher L.} and Kim, {Chai Wan} and Moon, {Young Ah} and Lisa Henry and Maya Palnitkar and McKean, {William B.} and Kevin Fitzgerald and Johann Deisenhofer and Horton, {Jay D.} and Kwon, {Hyock Joo}",
year = "2010",
month = "11",
day = "2",
doi = "10.1073/pnas.1012736107",
language = "English (US)",
volume = "107",
pages = "18820--18825",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "44",

}

TY - JOUR

T1 - Crystal structure of Spot 14, a modulator of fatty acid synthesis

AU - Colbert, Christopher L.

AU - Kim, Chai Wan

AU - Moon, Young Ah

AU - Henry, Lisa

AU - Palnitkar, Maya

AU - McKean, William B.

AU - Fitzgerald, Kevin

AU - Deisenhofer, Johann

AU - Horton, Jay D.

AU - Kwon, Hyock Joo

PY - 2010/11/2

Y1 - 2010/11/2

N2 - 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.

AB - 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.

KW - Lipogenesis

KW - Posttranslational

KW - Regulation

UR - http://www.scopus.com/inward/record.url?scp=78650505999&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650505999&partnerID=8YFLogxK

U2 - 10.1073/pnas.1012736107

DO - 10.1073/pnas.1012736107

M3 - Article

VL - 107

SP - 18820

EP - 18825

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 44

ER -