4NB5

Crystal Structure of a transcriptional regulator

4NB5 の概要

• エントリーDOI: 10.2210/pdb4nb5/pdb
• 分子名称: DNA binding protein, 1,3-dihydroxypropan-2-yl octadecanoate (3 entities in total)
• 機能のキーワード: dna binding, dna binding protein
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 77503.36

構造登録者

Su, C.-C.,Radhakrishnan, A.,Yu, E.W. (登録日: 2013-10-22, 公開日: 2014-04-23, 最終更新日: 2024-02-28)

主引用文献

Radhakrishnan, A.,Kumar, N.,Wright, C.C.,Chou, T.H.,Tringides, M.L.,Bolla, J.R.,Lei, H.T.,Rajashankar, K.R.,Su, C.C.,Purdy, G.E.,Yu, E.W.
Crystal Structure of the Transcriptional Regulator Rv0678 of Mycobacterium tuberculosis.
J.Biol.Chem., 289:16526-16540, 2014

PubMed Abstract: Recent work demonstrates that the MmpL (mycobacterial membrane protein large) transporters are dedicated to the export of mycobacterial lipids for cell wall biosynthesis. An MmpL transporter frequently works with an accessory protein, belonging to the MmpS (mycobacterial membrane protein small) family, to transport these key virulence factors. One such efflux system in Mycobacterium tuberculosis is the MmpS5-MmpL5 transporter. The expression of MmpS5-MmpL5 is controlled by the MarR-like transcriptional regulator Rv0678, whose open reading frame is located downstream of the mmpS5-mmpL5 operon. To elucidate the structural basis of Rv0678 regulation, we have determined the crystal structure of this regulator, to 1.64 Å resolution, revealing a dimeric two-domain molecule with an architecture similar to members of the MarR family of transcriptional regulators. Rv0678 is distinct from other MarR regulators in that its DNA-binding and dimerization domains are clustered together. These two domains seemingly cooperate to bind an inducing ligand that we identified as 2-stearoylglycerol, which is a fatty acid glycerol ester. The structure also suggests that the conformational change leading to substrate-mediated derepression is primarily caused by a rigid body rotational motion of the entire DNA-binding domain of the regulator toward the dimerization domain. This movement results in a conformational state that is incompatible with DNA binding. We demonstrate using electrophoretic mobility shift assays that Rv0678 binds to the mmpS5-mmpL5, mmpS4-mmpL4, and the mmpS2-mmpL2 promoters. Binding by Rv0678 was reversed upon the addition of the ligand. These findings provide new insight into the mechanisms of gene regulation in the MarR family of regulators.

PubMed: 24737322
DOI: 10.1074/jbc.M113.538959

実験手法

X-RAY DIFFRACTION (1.641 Å)