Zinc-binding to the cytoplasmic PAS domain regulates the essential WalK histidine kinase of Staphylococcus aureus
AuthorMonk, IR; Shaikh, N; Begg, SL; Gajdiss, M; Sharkey, LKR; Lee, JYH; Pidot, SJ; Seemann, T; Kuiper, M; Winnen, B; ...
Source TitleNATURE COMMUNICATIONS
PublisherNATURE PUBLISHING GROUP
University of Melbourne Author/sMcDevitt, Christopher; Monk, Ian; Neville, Stephanie; Sharkey, Liam; Lee, Jean; Pidot, Sacha; Seemann, Torsten; Howden, Benjamin; Stinear, Timothy; Udagedara, Saumya; ...
AffiliationMicrobiology and Immunology
Document TypeJournal Article
CitationsMonk, IR; Shaikh, N; Begg, SL; Gajdiss, M; Sharkey, LKR; Lee, JYH; Pidot, SJ; Seemann, T; Kuiper, M; Winnen, B; Hvorup, R; Collins, BM; Bierbaum, G; Udagedara, SR; Morey, JR; Pulyani, N; Howden, BP; Maher, MJ; McDevitt, CA; King, GF; Stinear, TP, Zinc-binding to the cytoplasmic PAS domain regulates the essential WalK histidine kinase of Staphylococcus aureus, NATURE COMMUNICATIONS, 2019, 10
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624279
WalKR (YycFG) is the only essential two-component regulator in the human pathogen Staphylococcus aureus. WalKR regulates peptidoglycan synthesis, but this function alone does not explain its essentiality. Here, to further understand WalKR function, we investigate a suppressor mutant that arose when WalKR activity was impaired; a histidine to tyrosine substitution (H271Y) in the cytoplasmic Per-Arnt-Sim (PASCYT) domain of the histidine kinase WalK. Introducing the WalKH271Y mutation into wild-type S. aureus activates the WalKR regulon. Structural analyses of the WalK PASCYT domain reveal a metal-binding site, in which a zinc ion (Zn2+) is tetrahedrally-coordinated by four amino acids including H271. The WalKH271Y mutation abrogates metal binding, increasing WalK kinase activity and WalR phosphorylation. Thus, Zn2+-binding negatively regulates WalKR. Promoter-reporter experiments using S. aureus confirm Zn2+ sensing by this system. Identification of a metal ligand recognized by the WalKR system broadens our understanding of this critical S. aureus regulon.
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