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PLoS Comput Biol. 2016 Apr 6;12(4):e1004862. doi: 10.1371/journal.pcbi.1004862. eCollection 2016 Apr.

Cache Domains That are Homologous to, but Different from PAS Domains Comprise the Largest Superfamily of Extracellular Sensors in Prokaryotes.

Author information

1
Genome Science and Technology Graduate Program, University of Tennessee-Oak Ridge National Laboratory, Knoxville, Tennessee, United States of America.
2
Department of Microbiology, University of Tennessee, Knoxville, Tennessee, United States of America.
3
Computer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States of America.
4
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.

Abstract

Cellular receptors usually contain a designated sensory domain that recognizes the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans. Although PAS domains were described as intracellular sensors, recent structural studies revealed PAS-like domains in extracytoplasmic regions in several transmembrane receptors. However, these structurally defined extracellular PAS-like domains do not match sequence-derived PAS domain models, and thus their distribution across the genomic landscape remains largely unknown. Here we show that structurally defined extracellular PAS-like domains belong to the Cache superfamily, which is homologous to, but distinct from the PAS superfamily. Our newly built computational models enabled identification of Cache domains in tens of thousands of signal transduction proteins including those from important pathogens and model organisms. Furthermore, we show that Cache domains comprise the dominant mode of extracellular sensing in prokaryotes.

PMID:
27049771
PMCID:
PMC4822843
DOI:
10.1371/journal.pcbi.1004862
[Indexed for MEDLINE]
Free PMC Article

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