PDBsum entry 4ja2

Signaling protein

PDB id: 4ja2

Contents

Protein chain

121 a.a.

Ligands

SO4

ACT ×2

Metals

_MG

Waters ×91

PDB id:

4ja2

Name:

Signaling protein

Title:

Structural basis of a rationally rewired protein-protein interface (rr468mutant v13p, l14i, i17m and n21v)

Structure:

Response regulator. Chain: a. Synonym: rr468, response regulator receiver protein. Engineered: yes. Mutation: yes

Source:

Thermotoga maritima. Organism_taxid: 243274. Strain: msb8. Gene: tm_0468. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.79Å R-factor: 0.188 R-free: 0.223

Authors:

A.I.Podgornaia,P.Casino,A.Marina,M.T.Laub

Key ref:

A.I.Podgornaia et al. (2013). Structural basis of a rationally rewired protein-protein interface critical to bacterial signaling. Structure, 21, 1636-1647. PubMed id: 23954504 DOI: 10.1016/j.str.2013.07.005

Date:

18-Feb-13 Release date: 04-Sep-13

Protein chain

Q9WYT9  (Q9WYT9_THEMA) -  Response regulator from Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8)

Seq: 122 a.a.

Struc: 121 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DOI no: 10.1016/j.str.2013.07.005

Structure 21:1636-1647 (2013)

PubMed id: 23954504

Structural basis of a rationally rewired protein-protein interface critical to bacterial signaling.

A.I.Podgornaia, P.Casino, A.Marina, M.T.Laub.

ABSTRACT

Two-component signal transduction systems typically involve a sensor histidine kinase that specifically phosphorylates a single, cognate response regulator. This protein-protein interaction relies on molecular recognition via a small set of residues in each protein. To better understand how these residues determine the specificity of kinase-substrate interactions, we rationally rewired the interaction interface of a Thermotoga maritima two-component system, HK853-RR468, to match that found in a different two-component system, Escherichia coli PhoR-PhoB. The rewired proteins interacted robustly with each other, but no longer interacted with the parent proteins. Analysis of the crystal structures of the wild-type and mutant protein complexes and a systematic mutagenesis study reveal how individual mutations contribute to the rewiring of interaction specificity. Our approach and conclusions have implications for studies of other protein-protein interactions and protein evolution and for the design of novel protein interfaces.