4YG1

HipB-O1-O2 complex/P21212 crystal form

4YG1 の概要

• エントリーDOI: 10.2210/pdb4yg1/pdb
• 関連するPDBエントリー: 4YG4 4YG7
• 分子名称: Antitoxin HipB, DNA (48-MER) (3 entities in total)
• 機能のキーワード: persistence, multidrug tolerance, hipa, transcription-dna complex, transcription/dna
• 由来する生物種: Escherichia coli (strain K12); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 62397.88

構造登録者

Schumacher, M.A. (登録日: 2015-02-25, 公開日: 2015-07-29, 最終更新日: 2023-09-27)

主引用文献

Schumacher, M.A.,Balani, P.,Min, J.,Chinnam, N.B.,Hansen, S.,Vulic, M.,Lewis, K.,Brennan, R.G.
HipBA-promoter structures reveal the basis of heritable multidrug tolerance.
Nature, 524:59-64, 2015

PubMed Abstract: Multidrug tolerance is largely responsible for chronic infections and caused by a small population of dormant cells called persisters. Selection for survival in the presence of antibiotics produced the first genetic link to multidrug tolerance: a mutant in the Escherichia coli hipA locus. HipA encodes a serine-protein kinase, the multidrug tolerance activity of which is neutralized by binding to the transcriptional regulator HipB and hipBA promoter. The physiological role of HipA in multidrug tolerance, however, has been unclear. Here we show that wild-type HipA contributes to persister formation and that high-persister hipA mutants cause multidrug tolerance in urinary tract infections. Perplexingly, high-persister mutations map to the N-subdomain-1 of HipA far from its active site. Structures of higher-order HipA-HipB-promoter complexes reveal HipA forms dimers in these assemblies via N-subdomain-1 interactions that occlude their active sites. High-persistence mutations, therefore, diminish HipA-HipA dimerization, thereby unleashing HipA to effect multidrug tolerance. Thus, our studies reveal the mechanistic basis of heritable, clinically relevant antibiotic tolerance.

PubMed: 26222023
DOI: 10.1038/nature14662

実験手法

X-RAY DIFFRACTION (3.25 Å)