Mycobacterium tuberculosis FasR senses long fatty acyl-CoA through a tunnel and a hydrophobic transmission spine.
Acyl Coenzyme A
/ chemistry
Allosteric Site
Bacterial Proteins
/ chemistry
Cell Wall
/ metabolism
Crystallography, X-Ray
DNA, Bacterial
/ chemistry
DNA-Binding Proteins
/ chemistry
Fatty Acids
/ metabolism
Ligands
Models, Molecular
Mycobacterium tuberculosis
/ metabolism
Protein Conformation
Transcription Factors
/ chemistry
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 07 2020
24 07 2020
Historique:
received:
20
06
2019
accepted:
30
06
2020
entrez:
26
7
2020
pubmed:
28
7
2020
medline:
9
9
2020
Statut:
epublish
Résumé
Mycobacterium tuberculosis is a pathogen with a unique cell envelope including very long fatty acids, implicated in bacterial resistance and host immune modulation. FasR is a TetR-like transcriptional activator that plays a central role in sensing mycobacterial long-chain fatty acids and regulating lipid biosynthesis. Here we disclose crystal structures of M. tuberculosis FasR in complex with acyl effector ligands and with DNA, uncovering its molecular sensory and switching mechanisms. A long tunnel traverses the entire effector-binding domain, enabling long fatty acyl effectors to bind. Only when the tunnel is entirely occupied, the protein dimer adopts a rigid configuration with its DNA-binding domains in an open state, leading to DNA dissociation. The protein-folding hydrophobic core connects the two domains, and is completed into a continuous spine when the effector binds. Such a transmission spine is conserved in a large number of TetR-like regulators, offering insight into effector-triggered allosteric functional control.
Identifiants
pubmed: 32710080
doi: 10.1038/s41467-020-17504-x
pii: 10.1038/s41467-020-17504-x
pmc: PMC7382501
doi:
Substances chimiques
Acyl Coenzyme A
0
Bacterial Proteins
0
DNA, Bacterial
0
DNA-Binding Proteins
0
Fatty Acids
0
Ligands
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3703Subventions
Organisme : NIAID NIH HHS
ID : R01 AI095183
Pays : United States
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