title: Mechanistic insights revealed by the crystal structure of a histidine kinase with signal transducer and sensor domains.
abstract: Two-component systems (TCSs) are important for the adaptation and survival of bacteria and fungi under stress conditions. A TCS is often composed of a membrane-bound sensor histidine kinase (SK) and a response regulator (RR), which are relayed through sequential phosphorylation steps. However, the mechanism for how an SK is switched on in response to environmental stimuli remains obscure. Here, we report the crystal structure of a complete cytoplasmic portion of an SK, VicK from Streptococcus mutans. The overall structure of VicK is a long-rod dimer that anchors four connected domains: HAMP, Per-ARNT-SIM (PAS), DHp, and catalytic and ATP binding domain (CA). The HAMP, a signal transducer, and the PAS domain, major sensor, adopt canonical folds with dyad symmetry. In contrast, the dimer of the DHp and CA domains is asymmetric because of different helical bends in the DHp domain and spatial positions of the CA domains. Moreover, a conserved proline, which is adjacent to the phosphoryl acceptor histidine, contributes to helical bending, which is essential for the autokinase and phosphatase activities. Together, the elegant architecture of VicK with a signal transducer and sensor domain suggests a model where DHp helical bending and a CA swing movement are likely coordinated for autokinase activation.
authors.affiliation: State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiangan, Xiamen, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Jiayan
authors.initials: J
authors.lastname: Sang
authors.forename: Jiawei
authors.initials: J
authors.lastname: Wang
authors.forename: Mingyan
authors.initials: M
authors.lastname: Su
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Downey
authors.forename: Qinggan
authors.initials: Q
authors.lastname: Wu
authors.forename: Shida
authors.initials: S
authors.lastname: Wang
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Cai
authors.forename: Xiaozheng
authors.initials: X
authors.lastname: Xu
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Dilani B
authors.initials: DB
authors.lastname: Senadheera
authors.forename: Dennis G
authors.initials: DG
authors.lastname: Cvitkovitch
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Steven D
authors.initials: SD
authors.lastname: Goodman
authors.forename: Aidong
authors.initials: A
authors.lastname: Han
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D000071677:Histidine Kinase; D011485:Protein Binding; D011494:Protein Kinases / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013295:Streptococcus mutans / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D011494:Protein Kinases; D000071677:Histidine Kinase