TY - JOUR
T1 - Structure and function of CarD, an essential mycobacterial transcription factor
AU - Srivastava, Devendra B.
AU - Leon, Katherine
AU - Osmundson, Joseph
AU - Garner, Ashley L.
AU - Weiss, Leslie A.
AU - Westblade, Lars F.
AU - Glickman, Michael S.
AU - Landick, Robert
AU - Darst, Seth A.
AU - Stallings, Christina L.
AU - Campbell, Elizabeth A.
PY - 2013/7/30
Y1 - 2013/7/30
N2 - 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.
AB - 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.
KW - Initiation
KW - Mycobacteria
KW - Ribosomal RNA (rRNA)
KW - Transcription activator
UR - http://www.scopus.com/inward/record.url?scp=84881092730&partnerID=8YFLogxK
U2 - 10.1073/pnas.1308270110
DO - 10.1073/pnas.1308270110
M3 - Article
C2 - 23858468
AN - SCOPUS:84881092730
VL - 110
SP - 12619
EP - 12624
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 31
ER -