PDBsum entry 4aih

Transcription

PDB id: 4aih

Contents

Protein chains

139 a.a.

131 a.a.

115 a.a.

Waters ×99

PDB id:

4aih

Name:

Transcription

Title:

Crystal structure of rova from yersinia in its free form

Structure:

Transcriptional regulator slya. Chain: a, b, c, d, e, f. Synonym: regulator of virulence protein a, transcriptional regulator for cryptic hemolysin, rova. Engineered: yes. Mutation: yes

Source:

Yersinia pseudotuberculosis. Organism_taxid: 502800. Strain: ypiii. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

2.40Å R-factor: 0.223 R-free: 0.266

Authors:

N.Quade,C.Mendonca,K.Herbst,A.K.Heroven,D.W.Heinz,P.Dersch

Key ref:

N.Quade et al. (2012). Structural basis for intrinsic thermosensing by the master virulence regulator RovA of Yersinia. J Biol Chem, 287, 35796-35803. PubMed id: 22936808

Date:

09-Feb-12 Release date: 12-Sep-12

Protein chains

B1JJ73  (SLYA_YERPY) -  Transcriptional regulator SlyA from Yersinia pseudotuberculosis serotype O:3 (strain YPIII)

Seq: 143 a.a.

Struc: 139 a.a.*

Protein chains

B1JJ73  (SLYA_YERPY) -  Transcriptional regulator SlyA from Yersinia pseudotuberculosis serotype O:3 (strain YPIII)

Seq: 143 a.a.

Struc: 131 a.a.*

Protein chain

B1JJ73  (SLYA_YERPY) -  Transcriptional regulator SlyA from Yersinia pseudotuberculosis serotype O:3 (strain YPIII)

Seq: 143 a.a.

Struc: 115 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

J Biol Chem 287:35796-35803 (2012)

PubMed id: 22936808

Structural basis for intrinsic thermosensing by the master virulence regulator RovA of Yersinia.

N.Quade, C.Mendonca, K.Herbst, A.K.Heroven, C.Ritter, D.W.Heinz, P.Dersch.

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.