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  • Molecular mechanism of interactions between ACAD9 and binding partners in mitochondrial respiratory complex I assembly.

Molecular mechanism of interactions between ACAD9 and binding partners in mitochondrial respiratory complex I assembly.

iScience (2021-10-15)
Chuanwu Xia, Baoying Lou, Zhuji Fu, Al-Walid Mohsen, Anna L Shen, Jerry Vockley, Jung-Ja P Kim
초록

The dual function protein ACAD9 catalyzes α,β-dehydrogenation of fatty acyl-CoA thioesters in fatty acid β-oxidation and is an essential chaperone for mitochondrial respiratory complex I (CI) assembly. ACAD9, ECSIT, and NDUFAF1 interact to form the core mitochondrial CI assembly complex. Current studies examine the molecular mechanism of ACAD9/ECSIT/NDUFAF1interactions. ACAD9 binds to the carboxy-terminal half and NDUFAF1 to the amino-terminal half of ECSIT. Binary complexes are unstable and aggregate easily, while the ACAD9/ECSIT/NDUFAF1 ternary complex is soluble and highly stable. Molecular modeling and small-angle X-ray scattering studies identified intra-complex interaction sites and binding sites for other assembly factors. Binding of ECSIT at the ETF binding site in the amino-terminal domain of ACAD9 is consistent with observed loss of FAD and enzymatic activity and demonstrates that the two functions of ACAD9 are mutually exclusive. Mapping of 42 known pathogenic mutations onto the homology-modeled ACAD9 structure provides structural insights into pathomechanisms of CI deficiency.

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Sigma-Aldrich
SUMO Protease, His tagged recombinant protein, lyophilized powder