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

Abstract

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 αCTD may play a role in Mtb transcription regulation. 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.

Authors:
; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
NIHNIGMS
OSTI Identifier:
1372250
Resource Type:
Journal Article
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 8; Journal Issue: 07, 2017; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
ENGLISH
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES

Citation Formats

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., 2017. 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. Thu . "Structural insights into the mycobacteria transcription initiation complex from analysis of X-ray crystal structures". United States. doi:10.1038/ncomms16072.
@article{osti_1372250,
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 αCTD may play a role in Mtb transcription regulation. 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},
issn = {2041-1723},
number = 07, 2017,
volume = 8,
place = {United States},
year = {2017},
month = {7}
}

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