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Title: Structural insights into the mycobacteria transcription initiation complex from analysis of X-ray crystal structures

The mycobacteria RNA polymerase (RNAP) is a target for antimicrobials against tuberculosis, motivating structure/function studies. Here we report a 3.2 Å-resolution crystal structure of a Mycobacterium smegmatis (Msm) open promoter complex (RPo), along with structural analysis of the Msm RPo and a previously reported 2.76 Å-resolution crystal structure of an Msm transcription initiation complex with a promoter DNA fragment. We observe the interaction of the Msm RNAP α-subunit C-terminal domain (αCTD) with DNA, and we provide evidence that the a CTD may play a role in Mtb transcription regulation. Here, our results reveal the structure of an Actinobacteria-unique insert of the RNAP β' subunit. Finally, our analysis reveals the disposition of the N-terminal segment of Msm σ A, which may comprise an intrinsically disordered protein domain unique to mycobacteria. The clade-specific features of the mycobacteria RNAP provide clues to the profound instability of mycobacteria RPo compared with E. coli.
Authors:
 [1] ;  [1] ;  [1] ;  [1]
  1. Rockefeller Univ., New York, NY (United States)
Publication Date:
Grant/Contract Number:
AC02-06CH11357; RO1 GM114450
Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 8; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Research Org:
Univ. of Chicago, IL (United States)
Sponsoring Org:
USDOE Office of Science (SC); National Institutes of Health (NIH)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES
OSTI Identifier:
1393440

Hubin, Elizabeth A., Lilic, Mirjana, Darst, Seth A., and Campbell, Elizabeth A.. Structural insights into the mycobacteria transcription initiation complex from analysis of X-ray crystal structures. United States: N. p., Web. doi:10.1038/ncomms16072.
Hubin, Elizabeth A., Lilic, Mirjana, Darst, Seth A., & Campbell, Elizabeth A.. Structural insights into the mycobacteria transcription initiation complex from analysis of X-ray crystal structures. United States. doi:10.1038/ncomms16072.
Hubin, Elizabeth A., Lilic, Mirjana, Darst, Seth A., and Campbell, Elizabeth A.. 2017. "Structural insights into the mycobacteria transcription initiation complex from analysis of X-ray crystal structures". United States. doi:10.1038/ncomms16072. https://www.osti.gov/servlets/purl/1393440.
@article{osti_1393440,
title = {Structural insights into the mycobacteria transcription initiation complex from analysis of X-ray crystal structures},
author = {Hubin, Elizabeth A. and Lilic, Mirjana and Darst, Seth A. and Campbell, Elizabeth A.},
abstractNote = {The mycobacteria RNA polymerase (RNAP) is a target for antimicrobials against tuberculosis, motivating structure/function studies. Here we report a 3.2 Å-resolution crystal structure of a Mycobacterium smegmatis (Msm) open promoter complex (RPo), along with structural analysis of the Msm RPo and a previously reported 2.76 Å-resolution crystal structure of an Msm transcription initiation complex with a promoter DNA fragment. We observe the interaction of the Msm RNAP α-subunit C-terminal domain (αCTD) with DNA, and we provide evidence that the a CTD may play a role in Mtb transcription regulation. Here, our results reveal the structure of an Actinobacteria-unique insert of the RNAP β' subunit. Finally, our analysis reveals the disposition of the N-terminal segment of Msm σA, which may comprise an intrinsically disordered protein domain unique to mycobacteria. The clade-specific features of the mycobacteria RNAP provide clues to the profound instability of mycobacteria RPo compared with E. coli.},
doi = {10.1038/ncomms16072},
journal = {Nature Communications},
number = ,
volume = 8,
place = {United States},
year = {2017},
month = {7}
}

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