Journal
STRUCTURE
Volume 21, Issue 9, Pages 1636-1647Publisher
CELL PRESS
DOI: 10.1016/j.str.2013.07.005
Keywords
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Funding
- NSF CAREER award [MCB-0844442]
- Ministerio de Ciencia e Innovacion [BIO2010-15424]
- Generalitat Valenciana [ACOMP2013/031]
- NSF Graduate Research Fellowship
- Ministry of Economy and Competitiveness
- European Community [283570]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [0844442] Funding Source: National Science Foundation
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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.
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