5U51

Structure of Francisella tularensis heterodimeric SspA (MglA-SspA) in complex with ppGpp

5U51 の概要

• エントリーDOI: 10.2210/pdb5u51/pdb
• 関連するPDBエントリー: 5U56
• 分子名称: Stringent starvation protein A, Macrophage growth locus A, GLYCEROL, ... (7 entities in total)
• 機能のキーワード: stringent starvation protein a, macrophage growth locus a, ppgpp, gst-fold, transcription
• 由来する生物種: Francisella tularensis; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 97601.20

構造登録者

Cuthbert, B.J.,Schumacher, M.A.,Brennan, R.G. (登録日: 2016-12-06, 公開日: 2017-08-16, 最終更新日: 2023-10-04)

主引用文献

Cuthbert, B.J.,Ross, W.,Rohlfing, A.E.,Dove, S.L.,Gourse, R.L.,Brennan, R.G.,Schumacher, M.A.
Dissection of the molecular circuitry controlling virulence in Francisella tularensis.
Genes Dev., 31:1549-1560, 2017

PubMed Abstract: the etiological agent of tularemia, is one of the most infectious bacteria known. Because of its extreme pathogenicity, is classified as a category A bioweapon by the US government. virulence stems from genes encoded on the pathogenicity island (FPI). An unusual set of regulators-the heteromeric macrophage growth locus protein A (MglA)-stringent starvation protein A (SspA) complex and the DNA-binding protein pathogenicity island gene regulator (PigR)-activates FPI transcription and thus is essential for virulence. Intriguingly, the second messenger, guanosine-tetraphosphate (ppGpp), which is produced during infection, is also involved in coordinating virulence; however, its role has been unclear. Here we identify MglA-SspA as a novel ppGpp-binding complex and describe structures of apo- and ppGpp-bound MglA-SspA. We demonstrate that MglA-SspA, which binds RNA polymerase (RNAP), also interacts with the C-terminal domain of PigR, thus anchoring the (MglA-SspA)-RNAP complex to the FPI promoter. Furthermore, we show that MglA-SspA must be bound to ppGpp to mediate high-affinity interactions with PigR. Thus, these studies unveil a novel pathway different from those described previously for regulation of transcription by ppGpp. The data also indicate that pathogenesis is controlled by a highly interconnected molecular circuitry in which the virulence machinery directly senses infection via a small molecule stress signal.

PubMed: 28864445
DOI: 10.1101/gad.303701.117

実験手法

X-RAY DIFFRACTION (2.8 Å)