4AIK

Crystal structure of RovA from Yersinia in complex with an invasin promoter fragment

4AIK の概要

• エントリーDOI: 10.2210/pdb4aik/pdb
• 関連するPDBエントリー: 4AIH 4AIJ
• 分子名称: TRANSCRIPTIONAL REGULATOR SLYA, ROVA PROMOTER FRAGMENT, 5'-D(*AP*TP*GP*AP*TP*AP*TP*TP *AP*TP**TP*TP*AP*TP*AP*TP*GP*AP*TP*AP*A)-3', ROVA PROMOTER FRAGMENT, 5'-D(*TP*TP*TP*AP*TP*CP*AP*TP *AP*TP*AP*AP*AP*TP*AP*AP*TP*AP*TP*CP*A)-3', ... (4 entities in total)
• 機能のキーワード: transcription, transcription factor, global regulator, virulence regulation, thermosensing
• 由来する生物種: YERSINIA PSEUDOTUBERCULOSIS; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 47340.99

構造登録者

Quade, N.,Mendonca, C.,Herbst, K.,Heroven, A.K.,Heinz, D.W.,Dersch, P. (登録日: 2012-02-10, 公開日: 2012-09-12, 最終更新日: 2023-12-20)

主引用文献

Quade, N.,Mendonca, C.,Herbst, K.,Heroven, A.K.,Ritter, C.,Heinz, D.W.,Dersch, P.
Structural Basis for Intrinsic Thermosensing by the Master Virulence Regulator Rova of Yersinia.
J.Biol.Chem., 287:35796-, 2012

PubMed Abstract: Pathogens often rely on thermosensing to adjust virulence gene expression. In yersiniae, important virulence-associated traits are under the control of the master regulator RovA, which uses a built-in thermosensor to control its activity. Thermal upshifts encountered upon host entry induce conformational changes in the RovA dimer that attenuate DNA binding and render the protein more susceptible to proteolysis. Here, we report the crystal structure of RovA in the free and DNA-bound forms and provide evidence that thermo-induced loss of RovA activity is promoted mainly by a thermosensing loop in the dimerization domain and residues in the adjacent C-terminal helix. These determinants allow partial unfolding of the regulator upon an upshift to 37 °C. This structural distortion is transmitted to the flexible DNA-binding domain of RovA. RovA contacts mainly the DNA backbone in a low-affinity binding mode, which allows the immediate release of RovA from its operator sites. We also show that SlyA, a close homolog of RovA from Salmonella with a very similar structure, is not a thermosensor and remains active and stable at 37 °C. Strikingly, changes in only three amino acids, reflecting evolutionary replacements in SlyA, result in a complete loss of the thermosensing properties of RovA and prevent degradation. In conclusion, only minor alterations can transform a thermotolerant regulator into a thermosensor that allows adjustment of virulence and fitness determinants to their thermal environment.

PubMed: 22936808
DOI: 10.1074/JBC.M112.379156

実験手法

X-RAY DIFFRACTION (1.85 Å)