Organization of the human mitochondrial transcription initiation complex

Yakubovskaya, Elena; Guja, Kip E.; Eng, Edward T.; Choi, Woo Suk; Mejia, Edison; Beglov, Dmitri; Lukin, Mark; Kozakov, Dima; Garcia-Diaz, Miguel

doi:10.1093/nar/gkt1360

Organization of the human mitochondrial transcription initiation complex

Journal Article · Thu Jan 09 00:00:00 EST 2014 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkt1360· OSTI ID:2469584

Yakubovskaya, Elena ^[1]; Guja, Kip E. ^[1]; Eng, Edward T. ^[1]; Choi, Woo Suk ^[1]; Mejia, Edison ^[1]; Beglov, Dmitri ^[1]; Lukin, Mark ^[1]; Kozakov, Dima ^[1]; Garcia-Diaz, Miguel ^[1]

Stony Brook University, NY (United States); New York Structural Biology Center, NY (United States); Boston University, MA (United States)

Initiation of transcription in human mitochondria involves two factors, TFAM and TFB2M, in addition to the mitochondrial RNA polymerase, POLRMT. We have investigated the organization of the human mitochondrial transcription initiation complex on the light-strand promoter (LSP) through solution X-ray scattering, electron microscopy (EM) and biochemical studies. Our EM results demonstrate a compact organization of the initiation complex, suggesting that protein–protein interactions might help mediate initiation. We demonstrate that, in the absence of DNA, only POLRMT and TFAM form a stable interaction, albeit one with low affinity. This is consistent with the expected transient nature of the interactions necessary for initiation and implies that the promoter DNA acts as a scaffold that enables formation of the full initiation complex. Docking of known crystal structures into our EM maps results in a model for transcriptional initiation that strongly correlates with new and existing biochemical observations. Our results reveal the organization of TFAM, POLRMT and TFB2M around the LSP and represent the first structural characterization of the entire mitochondrial transcriptional initiation complex.

View Accepted Manuscript (DOE)

Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE

Grant/Contract Number:: AC02-98CH10886

OSTI ID:: 2469584

Journal Information:: Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 6 Vol. 42; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

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