7CLA

Crystal structure of HTH-type transcriptional regulator SkgA from Caulobacter crescentus

7CLA の概要

• エントリーDOI: 10.2210/pdb7cla/pdb
• 分子名称: HTH-type transcriptional regulator SkgA (2 entities in total)
• 機能のキーワード: tipa-class protein, dna binding protein, merr-like transcriptional regulator, homodimer, transcription
• 由来する生物種: Caulobacter vibrioides (strain ATCC 19089 / CB15)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29968.80

構造登録者

Jiang, X.,Zhang, L.,Teng, M.,Li, X. (登録日: 2020-07-20, 公開日: 2020-10-28, 最終更新日: 2023-11-29)

主引用文献

Jiang, X.,Zhang, L.,Teng, M.,Li, X.
Antibiotic binding releases autoinhibition of the TipA multidrug-resistance transcriptional regulator.
J.Biol.Chem., 295:17865-17876, 2020

PubMed Abstract: Investigations of bacterial resistance strategies can aid in the development of new antimicrobial drugs as a countermeasure to the increasing worldwide prevalence of bacterial antibiotic resistance. One such strategy involves the TipA class of transcription factors, which constitute minimal autoregulated multidrug resistance (MDR) systems against diverse antibiotics. However, we have insufficient information regarding how antibiotic binding induces transcriptional activation to design molecules that could interfere with this process. To learn more, we determined the crystal structure of SkgA from Caulobacter crescentus as a representative TipA protein. We identified an unexpected spatial orientation and location of the antibiotic-binding TipAS effector domain in the apo state. We observed that the α6-α7 region of the TipAS domain, which is canonically responsible for forming the lid of antibiotic-binding cleft to tightly enclose the bound antibiotic, is involved in the dimeric interface and stabilized via interaction with the DNA-binding domain in the apo state. Further structural and biochemical analyses demonstrated that the unliganded TipAS domain sterically hinders promoter DNA binding but undergoes a remarkable conformational shift upon antibiotic binding to release this autoinhibition via a switch of its α6-α7 region. Hence, the promoters for MDR genes including tipA and RNA polymerases become available for transcription, enabling efficient antibiotic resistance. These insights into the molecular mechanism of activation of TipA proteins advance our understanding of TipA proteins, as well as bacterial MDR systems, and may provide important clues to block bacterial resistance.

PubMed: 33454020
DOI: 10.1074/jbc.RA120.016295

実験手法

X-RAY DIFFRACTION (2.5 Å)