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PMID: 18555780 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Rewiring the specificity of two-component signal transduction systems.

Cell ·Vol. 133 ·No. 6 ·2008-06-13 ·Pages 1043-54

Skerker JM, Perchuk BS, Siryaporn A, Lubin EA, Ashenberg O, Goulian M, Laub MT

Abstract

Two-component signal transduction systems are the predominant means by which bacteria sense and respond to environmental stimuli. Bacteria often employ tens or hundreds of these paralogous signaling systems, comprised of histidine kinases (HKs) and their cognate response regulators (RRs). Faithful transmission of information through these signaling pathways and avoidance of detrimental crosstalk demand exquisite specificity of HK-RR interactions. To identify the determinants of two-component signaling specificity, we examined patterns of amino acid coevolution in large, multiple sequence alignments of cognate kinase-regulator pairs. Guided by these results, we demonstrate that a subset of the coevolving residues is sufficient, when mutated, to completely switch the substrate specificity of the kinase EnvZ. Our results shed light on the basis of molecular discrimination in two-component signaling pathways, provide a general approach for the rational rewiring of these pathways, and suggest that analyses of coevolution may facilitate the reprogramming of other signaling systems and protein-protein interactions.

MeSH Terms
Amino Acid Sequence Bacterial Outer Membrane Proteins/chemistry,genetics,metabolism Bacterial Proteins/chemistry,genetics,metabolism Caulobacter crescentus/enzymology,metabolism Escherichia coli/enzymology,metabolism Escherichia coli Proteins/chemistry,genetics,metabolism Genes, Regulator Models, Molecular Molecular Sequence Data Multienzyme Complexes/chemistry,genetics,metabolism Mutagenesis Phosphorylation Protein Engineering Protein Structure, Tertiary Recombinant Fusion Proteins/chemistry,genetics,metabolism Signal Transduction Substrate Specificity Trans-Activators/chemistry,metabolism
Chemicals
Bacterial Outer Membrane Proteins Bacterial Proteins Escherichia coli Proteins Multienzyme Complexes Recombinant Fusion Proteins Trans-Activators osmolarity response regulator proteins envZ protein, E coli
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Skerker Jeffrey M
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Perchuk Barrett S
Siryaporn Albert
Lubin Emma A
Ashenberg Orr
Goulian Mark
Laub Michael T
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2008.04.040
Published
2008-06-13
Pages
1043-54
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2453690
Subset
IM
Grants
NIGMS NIH HHS · R01 GM080279-02 · United States
NIGMS NIH HHS · P50 GM068763 · United States
NIGMS NIH HHS · R01 GM082899-01 · United States
NIGMS NIH HHS · R01 GM082899 · United States
NIGMS NIH HHS · P50 GM068763-05 · United States
NIGMS NIH HHS · R01 GM080279 · United States
Corrections
CommentIn
PMID: 18555769
External Links
PubMed source DOI: 10.1016/j.cell.2008.04.040 PMC Full Text View journal details
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