期刊
JOURNAL OF MOLECULAR RECOGNITION
卷 26, 期 12, 页码 679-688出版社
WILEY
DOI: 10.1002/jmr.2313
关键词
Spot14; Mig12; acetyl-CoA carboxylase; protein-protein interactions; atomic force microscopy; Thrsp; silkworm Bombyx mori; fatty acid oxidation
资金
- National Institutes of Health
- Marriott Heart Disease Research Program, Mayo Clinic
- Young Research Overseas Dispatches Program for Accelerating Brain Circulation, Japan Society for the Promotion of Science
Acetyl-CoA carboxylase 2 (ACC2) is an isoform of ACC functioning as a negative regulator of fatty acid -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. (c) 2013 The Authors. Journal of Molecular Recognition published by John Wiley & Sons, Ltd.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据