Mycobacterium tuberculosis FasR senses long fatty acyl-CoA through a tunnel and a hydrophobic transmission spine.

Abstract:

: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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Lara J,Diacovich L,Trajtenberg F,Larrieux N,Malchiodi EL,Fernández MM,Gago G,Gramajo H,Buschiazzo A

doi

10.1038/s41467-020-17504-x

subject

Has Abstract

pub_date

2020-07-24 00:00:00

pages

3703

issue

1

issn

2041-1723

pii

10.1038/s41467-020-17504-x

journal_volume

11

pub_type

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