Structure and function of CarD, an essential mycobacterial transcription factor

Devendra B. Srivastava, Katherine Leon, Joseph Osmundson, Ashley L. Garner, Leslie A. Weiss, Lars F. Westblade, Michael S. Glickman, Robert Landick, Seth A. Darst, Christina L. Stallings, Elizabeth A. Campbell

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


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.

Original languageEnglish
Pages (from-to)12619-12624
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number31
StatePublished - Jul 30 2013


  • Initiation
  • Mycobacteria
  • Ribosomal RNA (rRNA)
  • Transcription activator


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