{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T20:54:50Z","timestamp":1760820890116,"version":"3.40.5"},"reference-count":65,"publisher":"American Society for Microbiology","issue":"18","license":[{"start":{"date-parts":[[2017,9,15]],"date-time":"2017-09-15T00:00:00Z","timestamp":1505433600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-13-BSV8-0002-01"],"award-info":[{"award-number":["ANR-13-BSV8-0002-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2017,9,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The whooping cough agent,\n            <jats:named-content content-type=\"genus-species\">Bordetella pertussis<\/jats:named-content>\n            , controls the expression of its large virulence regulon in a coordinated manner through the two-component system BvgAS. BvgS is a dimeric, multidomain sensor kinase. Each monomer comprises, in succession, tandem periplasmic Venus flytrap (VFT) domains, a transmembrane segment, a cytoplasmic Per-Arnt-Sim (PAS) domain, a kinase module, and additional phosphorelay domains. BvgS shifts between kinase and phosphatase modes of activity in response to chemical modulators that modify the clamshell motions of the VFT domains. We have shown previously that this regulation involves a shift between distinct states of conformation and dynamics of the two-helix coiled-coil linker preceding the enzymatic module. In this work, we determined the mechanism of signal transduction across the membrane via a first linker, which connects the VFT and PAS domains of BvgS, using extensive cysteine cross-linking analyses and other approaches. Modulator perception by the periplasmic domains appears to trigger a small, symmetrical motion of the transmembrane segments toward the periplasm, causing rearrangements of the noncanonical cytoplasmic coiled coil that follows. As a consequence, the interface of the PAS domains is modified, which affects the second linker and eventually causes the shift of enzymatic activity. The major features of this first linker are well conserved among BvgS homologs, indicating that the mechanism of signal transduction unveiled here is likely to be generally relevant for this family of sensor kinases.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            <jats:named-content content-type=\"genus-species\">Bordetella pertussis<\/jats:named-content>\n            produces virulence factors coordinately regulated by the two-component system BvgAS. BvgS is a sensor kinase, and BvgA is a response regulator that activates gene transcription when phosphorylated by BvgS. Sensor kinases homologous to BvgS are also found in other pathogens. Our goal is to decipher the mechanisms of BvgS signaling, since these sensor kinases may represent new targets for antibacterial agents. Signal perception by the sensor domains of BvgS triggers small motions of the helical linker region underneath. The protein domain that follows this linker undergoes a large conformational change that amplifies the initial signal, causing a shift of activity from kinase to phosphatase. Because BvgS homologs harbor similar regions, these signaling mechanisms are likely to apply generally to that family of sensor kinases.\n          <\/jats:p>","DOI":"10.1128\/jb.00114-17","type":"journal-article","created":{"date-parts":[[2017,5,16]],"date-time":"2017-05-16T00:50:19Z","timestamp":1494895819000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Conformational Changes of an Interdomain Linker Mediate Mechanical Signal Transmission in Sensor Kinase BvgS"],"prefix":"10.1128","volume":"199","author":[{"given":"Elodie","family":"Lesne","sequence":"first","affiliation":[{"name":"Universit\u00e9 Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL, Centre d'Infection et d'Immunit\u00e9 de Lille, Lille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elian","family":"Dupr\u00e9","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL, Centre d'Infection et d'Immunit\u00e9 de Lille, Lille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camille","family":"Locht","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL, Centre d'Infection et d'Immunit\u00e9 de Lille, Lille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudy","family":"Antoine","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL, Centre d'Infection et d'Immunit\u00e9 de Lille, Lille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5102-1704","authenticated-orcid":false,"given":"Fran\u00e7oise","family":"Jacob-Dubuisson","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL, Centre d'Infection et d'Immunit\u00e9 de Lille, Lille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2006.01.005"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3184\/003685006783238308"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.69.1.183"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2016.08.003"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.091208.073214"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(03)00156-2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004700"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(00)00070-9"},{"key":"e_1_3_3_10_2","first-page":"423","article-title":"Antigenic modulation of Bordetella pertussis","volume":"31","author":"Lacey BW","year":"1960","unstructured":"Lacey BW . 1960. Antigenic modulation of Bordetella pertussis. J Hyg (Lond) 31:423\u2013434.","journal-title":"J Hyg (Lond)"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.3.807-815.1993"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00781-06"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.655720"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006267107"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006996"},{"key":"e_1_3_3_16_2","first-page":"57","volume-title":"Two-component systems in bacteria","author":"Jacob-Dubuisson F","year":"2012","unstructured":"Jacob-Dubuisson F Wintjens R Herrou J Dupr\u00e9 E Antoine R . 2012. BvgS of pathogenic bordetellae: a paradigm for sensor-kinases with Venus flytrap perception domains, p 57\u201383. In Gross R Beier D (ed), Two-component systems in bacteria. Caister Academic Press, Norfolk, United Kingdom."},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2006.03.009"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3233(05)70004-8"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3095"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200300781"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2008.04.008"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2010.03.003"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2009.08.011"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-121809-151631"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.63.2.479-506.1999"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi801254c"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0620407"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2622"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-13-172"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02089-15"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2008.01.016"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3233(05)70003-6"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04875.x"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(07)23002-2"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1507217112"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2016.05.002"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2003.10.008"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2011.07812.x"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2009.06956.x"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808270106"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2015.04.002"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.12.017"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2011.11.014"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.06.058"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002878"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00616-15"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2014.04.019"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(00)01770-9"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2013.04.024"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1200479109"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2014.03.014"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001776"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001493"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.21422"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2009.07.015"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2007.09.014"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13118"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.174.3.970-979.1992"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.176.16.5163-5166.1994"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(94)90870-2"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1004823107"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.20.5902-5905.2000"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl158"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm404"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp033"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.849004"}],"container-title":["Journal of Bacteriology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JB.00114-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JB.00114-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T17:43:39Z","timestamp":1627580619000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JB.00114-17"}},"subtitle":[],"editor":[{"given":"Ann M.","family":"Stock","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2017,9,15]]},"references-count":65,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2017,9,15]]}},"alternative-id":["10.1128\/JB.00114-17"],"URL":"https:\/\/doi.org\/10.1128\/jb.00114-17","relation":{},"ISSN":["0021-9193","1098-5530"],"issn-type":[{"type":"print","value":"0021-9193"},{"type":"electronic","value":"1098-5530"}],"subject":[],"published":{"date-parts":[[2017,9,15]]},"assertion":[{"value":"2017-02-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-05-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-08-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}