6O6P

Structure of the regulator FasR from Mycobacterium tuberculosis in complex with DNA

Summary for 6O6P

• Entry DOI: 10.2210/pdb6o6p/pdb
• Descriptor: TetR family transcriptional regulator, DNA-forward, DNA-reverse (3 entities in total)
• Functional Keywords: tetr-like transcription factor, fatty acid biosynthesis regulation, transcription-dna complex, transcription/dna
• Biological source: Mycobacterium tuberculosis; More
• Total number of polymer chains: 4
• Total formula weight: 69931.13

Authors

Larrieux, N.,Trajtenberg, F.,Lara, J.,Gramajo, H.,Buschiazzo, A. (deposition date: 2019-03-07, release date: 2020-03-11, Last modification date: 2023-10-11)

Primary citation

Lara, J.,Diacovich, L.,Trajtenberg, F.,Larrieux, N.,Malchiodi, E.L.,Fernandez, M.M.,Gago, G.,Gramajo, H.,Buschiazzo, A.
Mycobacterium tuberculosis FasR senses long fatty acyl-CoA through a tunnel and a hydrophobic transmission spine.
Nat Commun, 11:3703-3703, 2020

PubMed 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.

PubMed: 32710080
DOI: 10.1038/s41467-020-17504-x

Experimental method

X-RAY DIFFRACTION (3.851 Å)