Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review

13 Scopus Citations
View graph of relations

Author(s)

  • Quanjiang Ji
  • Peter J. Chen
  • Guangrong Qin
  • Ziyang Hao
  • Zdzislaw Wawrzak
  • Won-Sik Yeo
  • Jenny Winjing Quang
  • Hoonsik Cho
  • Guan-Zheng Luo
  • Xiaocheng Weng
  • Qiancheng You
  • Chi-Hao Luan
  • Xiaojing Yang
  • Taeok Bae
  • Kunqian Yu
  • Hualiang Jiang
  • Chuan He

Detail(s)

Original languageEnglish
Article number11000
Journal / PublicationNature Communications
Volume7
Publication statusPublished - 18 Mar 2016
Externally publishedYes

Abstract

Most low GC Gram-positive bacteria possess an essential walKR two-component system (TCS) for signal transduction involved in regulating cell wall homoeostasis. Despite the well-established intracellular regulatory mechanism, the role of this TCS in extracellular signal recognition and factors that modulate the activity of this TCS remain largely unknown. Here we identify the extracellular receptor of the kinase 'WalK' (erWalK) as a key hub for bridging extracellular signal input and intracellular kinase activity modulation in Staphylococcus aureus. Characterization of the crystal structure of erWalK revealed a canonical Per-Arnt-Sim (PAS) domain for signal sensing. Single amino-acid mutation of potential signal-transduction residues resulted in severely impaired function of WalKR. A small molecule derived from structure-based virtual screening against erWalK is capable of selectively activating the walKR TCS. The molecular level characterization of erWalK will not only facilitate exploration of natural signal(s) but also provide a template for rational design of erWalK inhibitors.

Citation Format(s)

Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus. / Ji, Quanjiang; Chen, Peter J.; Qin, Guangrong; Deng, Xin; Hao, Ziyang; Wawrzak, Zdzislaw; Yeo, Won-Sik; Quang, Jenny Winjing; Cho, Hoonsik; Luo, Guan-Zheng; Weng, Xiaocheng; You, Qiancheng; Luan, Chi-Hao; Yang, Xiaojing; Bae, Taeok; Yu, Kunqian; Jiang, Hualiang; He, Chuan.

In: Nature Communications, Vol. 7, 11000, 18.03.2016.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review