Structural Basis of a Rationally Rewired Protein-Protein Interface Critical to Bacterial Signaling
Author(s)
Casino, Patricia; Marina, Alberto; Podgornaia, Anna Igorevna; Laub, Michael T
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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.
Date issued
2013-08Department
Massachusetts Institute of Technology. Computational and Systems Biology Program; Massachusetts Institute of Technology. Department of BiologyJournal
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
ISSN
0969-2126
1878-4186