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" |
