title: Bacterial Interactomes: Interacting Protein Partners Share Similar Function and Are Validated in Independent Assays More Frequently Than Previously Reported.
abstract: Numerous affinity purification-mass spectrometry (AP-MS) and yeast two-hybrid screens have each defined thousands of pairwise protein-protein interactions (PPIs), most of which are between functionally unrelated proteins. The accuracy of these networks, however, is under debate. Here, we present an AP-MS survey of the bacterium Desulfovibrio vulgaris together with a critical reanalysis of nine published bacterial yeast two-hybrid and AP-MS screens. We have identified 459 high confidence PPIs from D. vulgaris and 391 from Escherichia coli Compared with the nine published interactomes, our two networks are smaller, are much less highly connected, and have significantly lower false discovery rates. In addition, our interactomes are much more enriched in protein pairs that are encoded in the same operon, have similar functions, and are reproducibly detected in other physical interaction assays than the pairs reported in prior studies. Our work establishes more stringent benchmarks for the properties of protein interactomes and suggests that bona fide PPIs much more frequently involve protein partners that are annotated with similar functions or that can be validated in independent assays than earlier studies suggested.
authors.affiliation: From the Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720;
authors.forename: Maxim
authors.initials: M
authors.lastname: Shatsky
authors.affiliation: the Department of Obstetrics, Gynecology and Reproductive Sciences and Sandler-Moore Mass Spectrometry Core Facility, University of California at San Francisco, San Francisco, California, 94143;
authors.forename: Simon
authors.initials: S
authors.lastname: Allen
authors.affiliation: the Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720;
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Gold
authors.affiliation: the Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720;
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Liu
authors.affiliation: the Departments of Biochemistry and of Molecular Microbiology and Immunology, University of Missouri, Columbia, Missouri, 65211;
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Juba
authors.affiliation: From the Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720;
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Reveco
authors.affiliation: the Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, 37831;
authors.forename: Dwayne A
authors.initials: DA
authors.lastname: Elias
authors.affiliation: the Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720;
authors.forename: Ramadevi
authors.initials: R
authors.lastname: Prathapam
authors.affiliation: the Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720;
authors.forename: Jennifer
authors.initials: J
authors.lastname: He
authors.affiliation: the Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720;
authors.forename: Wenhong
authors.initials: W
authors.lastname: Yang
authors.affiliation: the Department of Obstetrics, Gynecology and Reproductive Sciences and Sandler-Moore Mass Spectrometry Core Facility, University of California at San Francisco, San Francisco, California, 94143;
authors.forename: Evelin D
authors.initials: ED
authors.lastname: Szakal
authors.affiliation: the Department of Obstetrics, Gynecology and Reproductive Sciences and Sandler-Moore Mass Spectrometry Core Facility, University of California at San Francisco, San Francisco, California, 94143;
authors.forename: Haichuan
authors.initials: H
authors.lastname: Liu
authors.affiliation: the Earth Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720;
authors.forename: Mary E
authors.initials: ME
authors.lastname: Singer
authors.affiliation: the Earth Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720;
authors.forename: Jil T
authors.initials: JT
authors.lastname: Geller
authors.affiliation: the Earth Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720;
authors.forename: Bonita R
authors.initials: BR
authors.lastname: Lam
authors.affiliation: the Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720;
authors.forename: Avneesh
authors.initials: A
authors.lastname: Saini
authors.affiliation: the Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720;
authors.forename: Valentine V
authors.initials: VV
authors.lastname: Trotter
authors.affiliation: the Department of Obstetrics, Gynecology and Reproductive Sciences and Sandler-Moore Mass Spectrometry Core Facility, University of California at San Francisco, San Francisco, California, 94143;
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hall
authors.affiliation: the Department of Obstetrics, Gynecology and Reproductive Sciences and Sandler-Moore Mass Spectrometry Core Facility, University of California at San Francisco, San Francisco, California, 94143;
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Fisher
authors.affiliation: From the Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720; the Department of Plant and Microbial Biology, University of California at Berkeley, Berkeley, California, 94720;
authors.forename: Steven E
authors.initials: SE
authors.lastname: Brenner
authors.affiliation: From the Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720;
authors.forename: Swapnil R
authors.initials: SR
authors.lastname: Chhabra
authors.affiliation: the Department of Civil and Environmental Engineering, University of Tennessee, Knoxville, Tennessee, 37996; and.
authors.forename: Terry C
authors.initials: TC
authors.lastname: Hazen
authors.affiliation: the Departments of Biochemistry and of Molecular Microbiology and Immunology, University of Missouri, Columbia, Missouri, 65211;
authors.forename: Judy D
authors.initials: JD
authors.lastname: Wall
authors.affiliation: the Department of Obstetrics, Gynecology and Reproductive Sciences and Sandler-Moore Mass Spectrometry Core Facility, University of California at San Francisco, San Francisco, California, 94143;
authors.forename: H Ewa
authors.initials: HE
authors.lastname: Witkowska
authors.affiliation: the Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Biggin
authors.affiliation: From the Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720; gpbutland@lbl.gov jmchandonia@lbl.gov.
authors.forename: John-Marc
authors.initials: JM
authors.lastname: Chandonia
authors.affiliation: the Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720; From the Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720; gpbutland@lbl.gov jmchandonia@lbl.gov.
authors.forename: Gareth
authors.initials: G
authors.lastname: Butland
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D002846:Chromatography, Affinity; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D016969:Desulfovibrio vulgaris / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D013058:Mass Spectrometry; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods; D020798:Two-Hybrid System Techniques
chemical_list: D001426:Bacterial Proteins