6PAJ

Structure of the SrrAB Histidine Kinase DHp-CA domain

6PAJ の概要

• エントリーDOI: 10.2210/pdb6paj/pdb
• 分子名称: Sensor protein SrrB, (4S)-2-METHYL-2,4-PENTANEDIOL (3 entities in total)
• 機能のキーワード: sensor protein, dimer, histidine kinase, membrane protein
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51927.38

構造登録者

Lopez Redondo, M.L.,Marina Moreno, A. (登録日: 2019-06-11, 公開日: 2020-04-22, 最終更新日: 2024-10-30)

主引用文献

Tiwari, N.,Lopez-Redondo, M.,Miguel-Romero, L.,Kulhankova, K.,Cahill, M.P.,Tran, P.M.,Kinney, K.J.,Kilgore, S.H.,Al-Tameemi, H.,Herfst, C.A.,Tuffs, S.W.,Kirby, J.R.,Boyd, J.M.,McCormick, J.K.,Salgado-Pabon, W.,Marina, A.,Schlievert, P.M.,Fuentes, E.J.
The SrrAB two-component system regulatesStaphylococcus aureuspathogenicity through redox sensitive cysteines.
Proc.Natl.Acad.Sci.USA, 117:10989-10999, 2020

PubMed Abstract: infections can lead to diseases that range from localized skin abscess to life-threatening toxic shock syndrome. The SrrAB two-component system (TCS) is a global regulator of virulence and critical for survival under environmental conditions such as hypoxic, oxidative, and nitrosative stress found at sites of infection. Despite the critical role of SrrAB in pathogenicity, the mechanism by which the SrrAB TCS senses and responds to these environmental signals remains unknown. Bioinformatics analysis showed that the SrrB histidine kinase contains several domains, including an extracellular Cache domain and a cytoplasmic HAMP-PAS-DHp-CA region. Here, we show that the PAS domain regulates both kinase and phosphatase enzyme activity of SrrB and present the structure of the DHp-CA catalytic core. Importantly, this structure shows a unique intramolecular cysteine disulfide bond in the ATP-binding domain that significantly affects autophosphorylation kinetics. In vitro data show that the redox state of the disulfide bond affects biofilm formation and toxic shock syndrome toxin-1 production. Moreover, with the use of the rabbit infective endocarditis model, we demonstrate that the disulfide bond is a critical regulatory element of SrrB function during infection. Our data support a model whereby the disulfide bond and PAS domain of SrrB sense and respond to the cellular redox environment to regulate survival and pathogenesis.

PubMed: 32354997
DOI: 10.1073/pnas.1921307117

実験手法

X-RAY DIFFRACTION (2 Å)