5D1W

Crystal structure of Mycobacterium tuberculosis Rv3249c transcriptional regulator.

5D1W の概要

• エントリーDOI: 10.2210/pdb5d1w/pdb
• 関連するPDBエントリー: 5D1R
• 分子名称: Rv3249c transcriptional regulator, PALMITIC ACID (2 entities in total)
• 機能のキーワード: mycobacterium tuberculosis, transcriptional regulator, transcription
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 142930.32

構造登録者

Chou, T.-H.,Delmar, J.,Su, C.-C.,Yu, E. (登録日: 2015-08-04, 公開日: 2015-09-30, 最終更新日: 2024-03-06)

主引用文献

Delmar, J.A.,Chou, T.H.,Wright, C.C.,Licon, M.H.,Doh, J.K.,Radhakrishnan, A.,Kumar, N.,Lei, H.T.,Bolla, J.R.,Rajashankar, K.R.,Su, C.C.,Purdy, G.E.,Yu, E.W.
Structural Basis for the Regulation of the MmpL Transporters of Mycobacterium tuberculosis.
J.Biol.Chem., 290:28559-28574, 2015

PubMed Abstract: The mycobacterial cell wall is critical to the virulence of these pathogens. Recent work shows that the MmpL (mycobacterial membrane protein large) family of transporters contributes to cell wall biosynthesis by exporting fatty acids and lipidic elements of the cell wall. The expression of the Mycobacterium tuberculosis MmpL proteins is controlled by a complex regulatory network, including the TetR family transcriptional regulators Rv3249c and Rv1816. Here we report the crystal structures of these two regulators, revealing dimeric, two-domain molecules with architecture consistent with the TetR family of regulators. Buried extensively within the C-terminal regulatory domains of Rv3249c and Rv1816, we found fortuitous bound ligands, which were identified as palmitic acid (a fatty acid) and isopropyl laurate (a fatty acid ester), respectively. Our results suggest that fatty acids may be the natural ligands of these regulatory proteins. Using fluorescence polarization and electrophoretic mobility shift assays, we demonstrate the recognition of promoter and intragenic regions of multiple mmpL genes by these proteins. Binding of palmitic acid renders these regulators incapable of interacting with their respective operator DNAs, which will result in derepression of the corresponding mmpL genes. Taken together, these experiments provide new perspectives on the regulation of the MmpL family of transporters.

PubMed: 26396194
DOI: 10.1074/jbc.M115.683797

実験手法

X-RAY DIFFRACTION (3.59 Å)