Crystal structure of a Mycobacterium smegmatis transcription initiation complex with RbpACrystal structure of a Mycobacterium smegmatis transcription initiation complex with RbpA

Structural highlights

5tw1 is a 11 chain structure with sequence from Aquifex aeolicus and Mycolicibacterium smegmatis MC2 155. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.76Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RBPA_MYCS2 Binds to RNA polymerase (RNAP), probably stimulating transcriptions from principal, but not alternative sigma factor promoters (By similarity). Partially restores transcription in the presence of rifampicin (Rif) in vitro; overexpression leads to an increase in the Rif tolerance in vivo, with smaller colonies. Seems to act by removing Rif from its binding site and preventing its further binding. No longer stimulates transcription in Rif-resistant RNA polymerase (with mutations in rpoB).[1] [2]

Publication Abstract from PubMed

RbpA and CarD are essential transcription regulators in mycobacteria. Mechanistic analyses of promoter open complex (RPo) formation establish thatRbpA and CarD cooperatively stimulate formation of anintermediate (RP2) leading to RPo; formation of RP2 islikely a bottleneck step at the majority of mycobacterial promoters. Once RPo forms, CarD also disfavors its isomerization back to RP2.We determined a 2.76 A-resolution crystal structure of a mycobacterial transcription initiation complex (TIC) with RbpA as well as a CarD/RbpA/TIC model. Both CarD and RbpA bind near the upstream edge of the -10 element where they likely facilitate DNA bending and impede transcription bubble collapse. In vivo studies demonstrate the essential role of RbpA, effects of RbpA truncations on transcription and cell physiology, and indicate additional functions for RbpA not evident in vitro. This work provides a framework to understand the control of mycobacterial transcriptionby RbpA and CarD.

Structure and function of the mycobacterial transcription initiation complex with the essential regulator RbpA.,Hubin EA, Fay A, Xu C, Bean JM, Saecker RM, Glickman MS, Darst SA, Campbell EA Elife. 2017 Jan 9;6. pii: e22520. doi: 10.7554/eLife.22520. PMID:28067618[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Dey A, Verma AK, Chatterji D. Role of an RNA polymerase interacting protein, MsRbpA, from Mycobacterium smegmatis in phenotypic tolerance to rifampicin. Microbiology. 2010 Mar;156(Pt 3):873-83. doi: 10.1099/mic.0.033670-0. Epub 2009, Nov 19. PMID:19926651 doi:http://dx.doi.org/10.1099/mic.0.033670-0
  2. Dey A, Verma AK, Chatterji D. Molecular insights into the mechanism of phenotypic tolerance to rifampicin conferred on mycobacterial RNA polymerase by MsRbpA. Microbiology. 2011 Jul;157(Pt 7):2056-71. doi: 10.1099/mic.0.047480-0. Epub 2011 , Mar 17. PMID:21415119 doi:http://dx.doi.org/10.1099/mic.0.047480-0
  3. Hubin EA, Fay A, Xu C, Bean JM, Saecker RM, Glickman MS, Darst SA, Campbell EA. Structure and function of the mycobacterial transcription initiation complex with the essential regulator RbpA. Elife. 2017 Jan 9;6. pii: e22520. doi: 10.7554/eLife.22520. PMID:28067618 doi:http://dx.doi.org/10.7554/eLife.22520

5tw1, resolution 2.76Å

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