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Structural Basis of a Rationally Rewired Protein-Protein Interface Critical to Bacterial Signaling

DOI: 10.1016/j.str.2013.07.005 DOI Help
PMID: 23954504 PMID Help

Authors: Anna I. Podgornaia (Massachusetts Institute of Technology) , Patricia Casino (Instituto de Biomedicina de Valencia (CSIC)) , Alberto Marina (Instituto de Biomedicina de Valencia (CSIC)) , Michael T. Laub (Massachusetts Institute of Technology)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Structure , VOL 21 (9) , PAGES 1636-47

State: Published (Approved)
Published: August 2013

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.

Journal Keywords: Amino; Bacterial; Catalytic; Crystallography; X-Ray; Escherichia; Models; Molecular; Protein; Quaternary; Protein; Secondary; Sequence; Amino; Signal; Thermotoga maritima

Subject Areas: Biology and Bio-materials


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)

Other Facilities: ID23-1, ID23-2 (ESRF)