Title | Structure and function of CarD, an essential mycobacterial transcription factor. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Srivastava DB, Leon K, Osmundson J, Garner AL, Weiss LA, Westblade LF, Glickman MS, Landick R, Darst SA, Stallings CL, Campbell EA |
Journal | Proc Natl Acad Sci U S A |
Volume | 110 |
Issue | 31 |
Pagination | 12619-24 |
Date Published | 2013 Jul 30 |
ISSN | 1091-6490 |
Keywords | Bacterial Proteins, DNA, Bacterial, Mycobacterium smegmatis, Mycobacterium tuberculosis, Promoter Regions, Genetic, Structure-Activity Relationship, Transcription Factors, Transcription, Genetic |
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 conformation where transcription bubble formation initiates. |
DOI | 10.1073/pnas.1308270110 |
Alternate Journal | Proc Natl Acad Sci U S A |
PubMed ID | 23858468 |
Grant List | AI64693 / AI / NIAID NIH HHS / United States |
Related Faculty:
Lars Westblade, Ph.D.