Spot14/Mig12 heterocomplex sequesters polymerization and restrains catalytic function of human acetyl-CoA carboxylase 2

Sungjo Park, In Wook Hwang, Yu Makishima, Ester Perales-Clemente, Tatsuya Kato, Nicolas J. Niederländer, Enoch Y. Park, Andre Terzic

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Acetyl-CoA carboxylase 2 (ACC2) is an isoform of ACC functioning as a negative regulator of fatty acid β-oxidation. Spot14, a thyroid hormone responsive protein, and Mig12, a Spot14 paralog, have recently been identified as regulators of fatty acid synthesis targeting ACC1, a distinctive subtype of ACC. Here, we examined whether Spot14/Mig12 modulates ACC2. Nanoscale protein topography mapped putative protein-protein interactions between purified human Spot14/Mig12 and ACC2, validated by functional assays. Human ACC2 displayed consistent enzymatic activity, and homogeneous particle distribution was probed by atomic force microscopy. Citrate-induced polymerization and enzymatic activity of ACC2 were restrained by the addition of the recombinant Spot14/Mig12 heterocomplex but only partially by the oligo-heterocomplex, demonstrating that the heterocomplex is a designated metabolic inhibitor of human ACC2. Moreover, Spot14/Mig12 demonstrated a sequestering role preventing an initial ACC2 nucleation step during filamentous polymer formation. Thus, the Spot14/Mig12 heterocomplex controls human ACC2 polymerization and catalytic function, emerging as a previously unrecognized molecular regulator in catalytic lipid metabolism.

Original languageEnglish (US)
Pages (from-to)679-688
Number of pages10
JournalJournal of Molecular Recognition
Volume26
Issue number12
DOIs
StatePublished - Dec 2013

Fingerprint

Acetyl-CoA Carboxylase
Polymerization
Proteins
Fatty Acids
Atomic Force Microscopy
Thyroid Hormones
Lipid Metabolism
Citric Acid
Polymers
Protein Isoforms
human ACACB protein

Keywords

  • acetyl-CoA carboxylase
  • atomic force microscopy
  • fatty acid oxidation
  • Mig12
  • protein-protein interactions
  • silkworm Bombyx mori
  • Spot14
  • Thrsp

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Spot14/Mig12 heterocomplex sequesters polymerization and restrains catalytic function of human acetyl-CoA carboxylase 2. / Park, Sungjo; Hwang, In Wook; Makishima, Yu; Perales-Clemente, Ester; Kato, Tatsuya; Niederländer, Nicolas J.; Park, Enoch Y.; Terzic, Andre.

In: Journal of Molecular Recognition, Vol. 26, No. 12, 12.2013, p. 679-688.

Research output: Contribution to journalArticle

Park, S, Hwang, IW, Makishima, Y, Perales-Clemente, E, Kato, T, Niederländer, NJ, Park, EY & Terzic, A 2013, 'Spot14/Mig12 heterocomplex sequesters polymerization and restrains catalytic function of human acetyl-CoA carboxylase 2', Journal of Molecular Recognition, vol. 26, no. 12, pp. 679-688. https://doi.org/10.1002/jmr.2313
Park, Sungjo ; Hwang, In Wook ; Makishima, Yu ; Perales-Clemente, Ester ; Kato, Tatsuya ; Niederländer, Nicolas J. ; Park, Enoch Y. ; Terzic, Andre. / Spot14/Mig12 heterocomplex sequesters polymerization and restrains catalytic function of human acetyl-CoA carboxylase 2. In: Journal of Molecular Recognition. 2013 ; Vol. 26, No. 12. pp. 679-688.
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