4JAS

Structural basis of a rationally rewired protein-protein interface (HK853mutant A268V, A271G, T275M, V294T and D297E and RR468mutant V13P, L14I, I17M and N21V)

Summary for 4JAS

• Entry DOI: 10.2210/pdb4jas/pdb
• Related: 4JA2 4JAU 4JAV
• Descriptor: Histidine kinase, Response regulator, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: bergerat fold, alpha/beta domain, signal transduction, autophosphorylation, phosphotransferase, dephosphorylation, histidine kinase, response regulator, phosphorylation, transferase-signaling protein complex, transferase/signaling protein
• Biological source: Thermotoga maritima; More
• Total number of polymer chains: 2
• Total formula weight: 43828.52

Authors

Podgornaia, A.I.,Casino, P.,Marina, A.,Laub, M.T. (deposition date: 2013-02-19, release date: 2013-09-04, Last modification date: 2024-10-16)

Primary citation

Podgornaia, A.I.,Casino, P.,Marina, A.,Laub, M.T.
Structural basis of a rationally rewired protein-protein interface critical to bacterial signaling
Structure, 21:1636-1647, 2013

PubMed 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.

PubMed: 23954504
DOI: 10.1016/j.str.2013.07.005

Experimental method

X-RAY DIFFRACTION (3 Å)