Identification of a Molecular Latch that Regulates Staphylococcal Virulence.
Allosteric Regulation
Bacterial Proteins
/ chemistry
Humans
Hydrogen Bonding
Molecular Docking Simulation
Peptides, Cyclic
/ metabolism
Protein Conformation
Protein Kinases
/ chemistry
Quorum Sensing
Signal Transduction
Staphylococcal Infections
/ microbiology
Staphylococcus aureus
/ chemistry
Virulence
Staphylococcus aureus
agr interference
allosteric regulation
autoinducing peptides
biofilm formation
conformational equilibrium
constitutive mutations
docking interaction
protein histidine kinase AgrC
quorum sensing
Journal
Cell chemical biology
ISSN: 2451-9448
Titre abrégé: Cell Chem Biol
Pays: United States
ID NLM: 101676030
Informations de publication
Date de publication:
18 04 2019
18 04 2019
Historique:
received:
04
06
2018
revised:
27
11
2018
accepted:
10
01
2019
pubmed:
19
2
2019
medline:
28
1
2020
entrez:
19
2
2019
Statut:
ppublish
Résumé
Virulence induction in the Staphylococcus aureus is under the control of a quorum sensing (QS) circuit encoded by the accessory gene regulator (agr) locus. Allelic variation within agr produces four QS specificity groups, each producing a unique secreted autoinducer peptide (AIP) and receptor histidine kinase (RHK), AgrC. Cognate AIP-AgrC interactions activate virulence through a two-component signaling cascade, whereas non-cognate pairs are generally inhibitory. Here we pinpoint a key hydrogen-bonding interaction within AgrC that acts as a switch to convert helical motions propagating from the receptor sensor domain into changes in inter-domain association within the kinase module. AgrC mutants lacking this interaction are constitutively active in vitro and in vivo, the latter leading to a pronounced attenuation of S. aureus biofilm formation. Thus, our work sheds light on the regulation of this biomedically important RHK.
Identifiants
pubmed: 30773482
pii: S2451-9456(19)30028-5
doi: 10.1016/j.chembiol.2019.01.006
pmc: PMC6506218
mid: NIHMS1519071
pii:
doi:
Substances chimiques
AgrD protein, Staphylococcus
0
Bacterial Proteins
0
Peptides, Cyclic
0
Protein Kinases
EC 2.7.-
AgrC protein, Staphylococcus
EC 2.7.3.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
548-558.e4Subventions
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM103485
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI042783
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM095880
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
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