TY - JOUR
T1 - Spot14/Mig12 heterocomplex sequesters polymerization and restrains catalytic function of human acetyl-CoA carboxylase 2
AU - Park, Sungjo
AU - Hwang, In Wook
AU - Makishima, Yu
AU - Perales-Clemente, Ester
AU - Kato, Tatsuya
AU - Niederländer, Nicolas J.
AU - Park, Enoch Y.
AU - Terzic, Andre
PY - 2013/12
Y1 - 2013/12
N2 - 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.
AB - 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.
KW - Mig12
KW - Spot14
KW - Thrsp
KW - acetyl-CoA carboxylase
KW - atomic force microscopy
KW - fatty acid oxidation
KW - protein-protein interactions
KW - silkworm Bombyx mori
UR - http://www.scopus.com/inward/record.url?scp=84888627816&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84888627816&partnerID=8YFLogxK
U2 - 10.1002/jmr.2313
DO - 10.1002/jmr.2313
M3 - Article
C2 - 24277613
AN - SCOPUS:84888627816
SN - 0952-3499
VL - 26
SP - 679
EP - 688
JO - Journal of Molecular Recognition
JF - Journal of Molecular Recognition
IS - 12
ER -