Spot14/Mig12 Heterocomplex Sequesters Polymerization and Restrains Catalytic Function of Human Acetyl-CoA Carboxylase 2

Overview

Journal J Mol Recognit

Specialty Molecular Biology

Date 2013 Nov 27

PMID 24277613

Citations 14

Authors

Sungjo Park

In-Wook Hwang

Yu Makishima

Ester Perales-Clemente

Tatsuya Kato

Nicolas J Niederlander

Enoch Y Park

Andre Terzic

Affiliations

Soon will be listed here.

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.

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