Structural Basis of a Rationally Rewired Protein-Protein Interface Critical to Bacterial Signaling
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Laub_Structural basis.pdf
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3.98 MB
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Author(s)
Casino, Patricia
Marina, Alberto
Podgornaia, Anna Igorevna
Laub, Michael T
Date Issued
August 2013
Journal
Structure
Publisher
Elsevier
Citation
Podgornaia, Anna I.; Casino, Patricia; Marina, Alberto and Laub, Michael T. “Structural Basis of a Rationally Rewired Protein-Protein Interface Critical to Bacterial Signaling.” Structure 21, no. 9 (September 2013): 1636–1647 © 2013 Elsevier Ltd
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Computational and Systems Biology Program
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.str.2013.07.005
