3R1F

Crystal structure of a key regulator of virulence in Mycobacterium tuberculosis

3R1F の概要

• エントリーDOI: 10.2210/pdb3r1f/pdb
• 分子名称: ESX-1 secretion-associated regulator EspR (2 entities in total)
• 機能のキーワード: helix-turn-helix, transcription factor, helix-turn-helix transcription factor, transcription
• 由来する生物種: Mycobacterium tuberculosis
• 細胞内の位置: Secreted: P96228
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 273393.04

構造登録者

Rosenberg, O.S.,Dovey, C.,Finer-Moore, J.,Stroud, R.M.,Cox, J.S. (登録日: 2011-03-10, 公開日: 2011-08-03, 最終更新日: 2024-10-16)

主引用文献

Rosenberg, O.S.,Dovey, C.,Tempesta, M.,Robbins, R.A.,Finer-Moore, J.S.,Stroud, R.M.,Cox, J.S.
EspR, a key regulator of Mycobacterium tuberculosis virulence, adopts a unique dimeric structure among helix-turn-helix proteins.
Proc.Natl.Acad.Sci.USA, 108:13450-13455, 2011

PubMed Abstract: EspR is a transcriptional regulator that activates the ESX-1 secretion system during Mycobacterium tuberculosis infection and is critical for pathogenesis. It is unique among DNA-binding proteins as it is secreted as part of a feedback regulatory loop that serves to mitigate transcriptional activity. Here we report the crystal structure of a functional EspR dimer at 2.5-Å resolution. The amino-terminal half of EspR is a helix-turn-helix (HTH) DNA-binding domain and the carboxy terminus consists of a dimerization domain with similarity to the SinR:SinI sporulation regulator of Bacillus subtilis. Surprisingly, the HTH domains of EspR are arranged in an unusual conformation in which they are splayed at an oblique angle to each other, suggesting that EspR binds DNA in a profoundly different way than most other known HTH regulators. By mapping the EspR binding sites in the espACD promoter, using both in vivo and in vitro binding assays, we show that the EspR operators are located unusually far from the promoter. The EspR dimer binds to these sites cooperatively, but the two "half-sites" contacted by each DNA recognition motif are separated by 177 base pairs. The distinctive structure of EspR and the exceptional arrangement of its operator contacts suggest that it could promote DNA looping in its target promoter. We hypothesize that direct DNA looping mediated by single-site binding of each EspR monomer may facilitate transcriptional control of this important virulence system.

PubMed: 21795602
DOI: 10.1073/pnas.1110242108

実験手法

X-RAY DIFFRACTION (2.5 Å)