Dataset Information

Conformational dynamics of the essential sensor histidine kinase WalK.

ABSTRACT: Two-component systems (TCSs) are key elements in bacterial signal transduction in response to environmental stresses. TCSs generally consist of sensor histidine kinases (SKs) and their cognate response regulators (RRs). Many SKs exhibit autokinase, phosphoryltransferase and phosphatase activities, which regulate RR activity through a phosphorylation and dephosphorylation cycle. However, how SKs perform different enzymatic activities is poorly understood. Here, several crystal structures of the minimal catalytic region of WalK, an essential SK from Lactobacillus plantarum that shares 60% sequence identity with its homologue VicK from Streptococcus mutans, are presented. WalK adopts an asymmetrical closed structure in the presence of ATP or ADP, in which one of the CA domains is positioned close to the DHp domain, thus leading both the ?- and ?-phosphates of ATP/ADP to form hydrogen bonds to the ?- but not the ?-nitrogen of the phosphorylatable histidine in the DHp domain. In addition, the DHp domain in the ATP/ADP-bound state has a 25.7° asymmetrical helical bending coordinated with the repositioning of the CA domain; these processes are mutually exclusive and alternate in response to helicity changes that are possibly regulated by upstream signals. In the absence of ATP or ADP, however, WalK adopts a completely symmetric open structure with its DHp domain centred between two outward-reaching CA domains. In summary, these structures of WalK reveal the intrinsic dynamic properties of an SK structure as a molecular basis for multifunctionality.

SUBMITTER: Cai Y

PROVIDER: S-EPMC5633905 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Conformational dynamics of the essential sensor histidine kinase WalK.

Cai Yongfei Y Su Mingyang M Ahmad Ashfaq A Hu Xiaojie X Sang Jiayan J Kong Lingyuan L Chen Xingqiang X Wang Chen C Shuai Jianwei J Han Aidong A

Acta crystallographica. Section D, Structural biology 20170927 Pt 10

Two-component systems (TCSs) are key elements in bacterial signal transduction in response to environmental stresses. TCSs generally consist of sensor histidine kinases (SKs) and their cognate response regulators (RRs). Many SKs exhibit autokinase, phosphoryltransferase and phosphatase activities, which regulate RR activity through a phosphorylation and dephosphorylation cycle. However, how SKs perform different enzymatic activities is poorly understood. Here, several crystal structures of the m ...[more]

PMID: 28994408

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Project description:VxrA and VxrB are cognate histidine kinase (HK) - response regulator (RR) pairs of a two-component signaling system (TCS) found in Vibrio cholerae, a bacterial pathogen that causes cholera. The VxrAB TCS positively regulates virulence, the Type VI Secretion System, biofilm formation, and cell wall homeostasis in V. cholerae, providing protection from environmental stresses and contributing to the transmission and virulence of the pathogen. The VxrA HK has a unique periplasmic sensor domain (SD) and, remarkably, lacks a cytoplasmic linker domain between the second transmembrane helix and the dimerization and histidine phosphotransfer (DHp) domain, indicating that this system may utilize a potentially unique signal sensing and transmission TCS mechanism. In this study, we have determined several crystal structures of VxrA-SD and its mutants. These structures reveal a novel structural fold forming an unusual β hairpin-swapped dimer. A conformational change caused by relative rotation of the two monomers in a VxrA-SD dimer could potentially change the association of transmembrane helices and, subsequently, the pairing of cytoplasmic DHp domains. Based on the structural observation, we propose a putative scissor-like closing regulation mechanism for the VxrA HK.IMPORTANCE V. cholerae has a dynamic life cycle, which requires rapid adaptation to changing external conditions. Two-component signal transduction (TCS) systems allow V. cholerae to sense and respond to these environmental changes. The VxrAB TCS positively regulates a number of important V. cholerae phenotypes, including virulence, the Type Six Secretion System, biofilm formation, and cell wall homeostasis. Here, we provide the crystal structure of the VxrA sensor histidine kinase sensing domain and propose a mechanism for signal transduction. The cognate signal for VxrAB remains unknown, however, in this work we couple our structural analysis with functional assessments of key residues to further our understanding of this important TCS.

Dataset Information

Conformational dynamics of the essential sensor histidine kinase WalK.

Publications

Conformational dynamics of the essential sensor histidine kinase WalK.

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