6D2S

Mycobacterium tuberculosis transcriptional regulator

6D2S の概要

• エントリーDOI: 10.2210/pdb6d2s/pdb
• 関連するPDBエントリー: 6CYJ 6CYY 6CZ6
• 分子名称: HTH-type transcriptional regulator PrpR, CALCIUM ION, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: 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: 1
• 化学式量合計: 32755.92

構造登録者

Tang, S.,Sacchettini, J. (登録日: 2018-04-13, 公開日: 2019-04-17, 最終更新日: 2023-10-04)

主引用文献

Tang, S.,Hicks, N.D.,Cheng, Y.S.,Silva, A.,Fortune, S.M.,Sacchettini, J.C.
Structural and functional insight into the Mycobacterium tuberculosis protein PrpR reveals a novel type of transcription factor.
Nucleic Acids Res., 47:9934-9949, 2019

PubMed Abstract: The pathogenicity of Mycobacterium tuberculosis depends upon its ability to catabolize host cholesterol. Upregulation of the methylcitrate cycle (MCC) is required to assimilate and detoxify propionyl-CoA, a cholesterol degradation product. The transcription of key genes prpC and prpD in MCC is activated by MtPrpR, a member of a family of prokaryotic transcription factors whose structures and modes of action have not been clearly defined. We show that MtPrpR has a novel overall structure and directly binds to CoA or short-chain acyl-CoA derivatives to form a homotetramer that covers the binding cavity and locks CoA tightly inside the protein. The regulation of this process involves a [4Fe4S] cluster located close to the CoA-binding cavity on a neighboring chain. Mutations in the [4Fe4S] cluster binding residues rendered MtPrpR incapable of regulating MCC gene transcription. The structure of MtPrpR without the [4Fe4S] cluster-binding region shows a conformational change that prohibits CoA binding. The stability of this cluster means it is unlikely a redox sensor but may function by sensing ambient iron levels. These results provide mechanistic insights into this family of critical transcription factors who share similar structures and regulate gene transcription using a combination of acyl-CoAs and [4Fe4S] cluster.

PubMed: 31504787
DOI: 10.1093/nar/gkz724

実験手法

X-RAY DIFFRACTION (1.819 Å)