Structure and function of CarD, an essential mycobacterial transcription factor Journal Article


Authors: Srivastava, D. B.; Leon, K.; Osmundson, J.; Garner, A. L.; Weiss, L. A.; Westblade, L. F.; Glickman, M. S.; Landick, R.; Darst, S. A.; Stallings, C. L.; Campbell, E. A.
Article Title: Structure and function of CarD, an essential mycobacterial transcription factor
Abstract: CarD, an essential transcription regulator in Mycobacterium tuberculosis, directly interacts with the RNA polymerase (RNAP). We used a combination of in vivo and in vitro approaches to establish that CarD is a global regulator that stimulates the formation of RNAP-holoenzyme open promoter (RPo) complexes. We determined the X-ray crystal structure of Thermus thermophilus CarD, allowing us to generate a structural model of the CarD/RPo complex. On the basis of our structural and functional analyses, we propose that CarD functions by forming protein/protein and protein/DNA interactions that bridge the RNAP to the promoter DNA. CarD appears poised to interact with a DNA structure uniquely presented by the RPo: the splayed minor groove at the double-stranded/single- stranded DNA junction at the upstream edge of the transcription bubble. Thus, CarD uses an unusual mechanism for regulating transcription, sensing the DNA conformationwhere transcription bubble formation initiates. © PNAS 2013.
Keywords: controlled study; unclassified drug; promoter region; nonhuman; protein function; transcription factor; in vitro study; bacterial protein; mycobacterium tuberculosis; transcription regulation; crystal structure; dna structure; protein structure; protein dna interaction; thermus thermophilus; dna conformation; initiation; mycobacteria; holoenzyme; ribosomal rna (rrna); transcription activator; card protein
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 110
Issue: 31
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2013-07-30
Start Page: 12619
End Page: 12624
Language: English
DOI: 10.1073/pnas.1308270110
PROVIDER: scopus
PMCID: PMC3732983
PUBMED: 23858468
DOI/URL:
Notes: --- - "Export Date: 4 September 2013" - "CODEN: PNASA" - "Source: Scopus"
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  1. Michael Glickman
    110 Glickman