Proteobacterial Origin of Protein Arginine Methylation and Regulation of Complex I Assembly by MidA
AuthorsShahul Hameed, Umar F.
Lay, Sui T.
Annesley, Sarah J.
Fisher, Paul R.
Arold, Stefan T.
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Computational Bioscience Research Center (CBRC)
Online Publication Date2018-08-24
Print Publication Date2018-08
Permanent link to this recordhttp://hdl.handle.net/10754/628476
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AbstractThe human protein arginine methyltransferase NDUFAF7 controls the assembly of the ∼1-MDa mitochondrial complex I (CI; the NADH ubiquinone oxidoreductase) by methylating its subunit NDUFS2. We determined crystal structures of MidA, the Dictyostelium ortholog of NDUFAF7. The MidA catalytic core domain resembles other eukaryotic methyltransferases. However, three large core loops assemble into a regulatory domain that is likely to control ligand selection. Binding of MidA to NDUFS2 is weakened by methylation, suggesting a mechanism for methylation-controlled substrate release. Structural and bioinformatic analyses support that MidA and NDUFAF7 and their role in CI assembly are conserved from bacteria to humans, implying that protein methylation already existed in proteobacteria. In vivo studies confirmed the critical role of the MidA methyltransferase activity for CI assembly, growth, and phototaxis of Dictyostelium. Collectively, our data elucidate the origin of protein arginine methylation and its use by MidA/NDUFAF7 to regulate CI assembly.
CitationShahul Hameed UF, Sanislav O, Lay ST, Annesley SJ, Jobichen C, et al. (2018) Proteobacterial Origin of Protein Arginine Methylation and Regulation of Complex I Assembly by MidA. Cell Reports 24: 1996–2004. Available: http://dx.doi.org/10.1016/j.celrep.2018.07.075.
SponsorsWe acknowledge SOLEIL for the provision of synchrotron radiation facilities, and we would like to thank L. Chavas, P. Legrand, S. Sirigu, and P. Montaville for assistance in using beamline PROXIMA 1; G. Fox, M. Savko, and B. Shepard for assistance in using beamline PROXIMA 2A; and J. Perez and A. Thureau for assistance in using the beamline SWING. We also acknowledge the National Synchrotron Radiation Research Centre beamline 13B1 of the Taiwan Synchrotron Facility for X-ray data collection. We thank the KAUST Bioscience Core Labs for their support. This research was supported by the King Abdullah University of Science and Technology (KAUST) and the Academic Research Fund (FRC) of the Ministry of Education, Singapore (to K.S.).
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