title: Cache Domains That are Homologous to, but Different from PAS Domains Comprise the Largest Superfamily of Extracellular Sensors in Prokaryotes.
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.
authors.affiliation: Genome Science and Technology Graduate Program, University of Tennessee-Oak Ridge National Laboratory, Knoxville, Tennessee, United States of America.|Department of Microbiology, University of Tennessee, Knoxville, Tennessee, United States of America.|Computer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States of America.
authors.forename: Amit A
authors.initials: AA
authors.lastname: Upadhyay
authors.affiliation: Department of Microbiology, University of Tennessee, Knoxville, Tennessee, United States of America.|Computer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States of America.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Fleetwood
authors.affiliation: Genome Science and Technology Graduate Program, University of Tennessee-Oak Ridge National Laboratory, Knoxville, Tennessee, United States of America.|Department of Microbiology, University of Tennessee, Knoxville, Tennessee, United States of America.|Computer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States of America.
authors.forename: Ogun
authors.initials: O
authors.lastname: Adebali
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Finn
authors.affiliation: Genome Science and Technology Graduate Program, University of Tennessee-Oak Ridge National Laboratory, Knoxville, Tennessee, United States of America.|Department of Microbiology, University of Tennessee, Knoxville, Tennessee, United States of America.|Computer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States of America.
authors.forename: Igor B
authors.initials: IB
authors.lastname: Zhulin
mesh_terms: D000465:Algorithms; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D019295:Computational Biology; D019143:Evolution, Molecular; D008390:Markov Chains; D008958:Models, Molecular; D010802:Phylogeny; D011387:Prokaryotic Cells / Q000737:chemistry; D017434:Protein Structure, Tertiary / Q000235:genetics; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics; D015398:Signal Transduction
chemical_list: D019843:Archaeal Proteins; D001426:Bacterial Proteins; D011956:Receptors, Cell Surface