5is1 | pdb_00005is1
Crystal structure of the extracellular domain of sensor histidine kinase YycG from Staphylococcus aureus at 2.0 Angstrom resolution
Structural highlights
FunctionWALK_STAA8 Member of the two-component regulatory system WalK/WalR that regulates genes involved in cell wall metabolism, virulence regulation, biofilm production, oxidative stress resistance and antibiotic resistance via direct or indirect regulation of autolysins (PubMed:14762013, PubMed:17827301, PubMed:22825451). Functions as a sensor protein kinase which is autophosphorylated at a histidine residue in the dimerization domain and transfers its phosphate group to the conserved aspartic acid residue in the regulatory domain of WalR. In turn, WalR binds to the upstream promoter regions of the target genes to positively and negatively regulate their expression (PubMed:14762013, PubMed:22825451).[1] [2] [3] Publication Abstract from PubMedBacterial two-component signal transduction systems are used to adapt to fluctuations in the environment. YycG, a key two-component histidine kinase in Staphylococcus aureus, plays an essential role in cell viability and regulates cell wall metabolism, biofilm formation, virulence, and antibiotic resistance. For these reasons, YycG is considered a compelling target for the development of novel antibiotics. However, to date, the signaling mechanism of YycG and its stimulus are poorly understood mainly because of a lack of structural information on YycG. To address this deficiency, we determined the crystal structure of the extracellular domain of S. aureus YycG (YycGex) at 2.0-A resolution. The crystal structure indicated two subunits with an extracellular Per-Arnt-Sim (PAS) topology packed into a dimer with interloop interactions. Disulfide scanning using cysteine-substituted mutants revealed that YycGex possessed dimeric interfaces not only in the loop but also in the helix alpha1. Cross-linking studies using intact YycG demonstrated that it was capable of forming high molecular weight oligomers on the cell membrane. Furthermore, we also observed that two auxiliary proteins of YycG, YycH and YycI, cooperatively interfered with the multimerization of YycG. From these results, we propose that signaling through YycG is regulated by multimerization and binding of YycH and YycI. These structural studies, combined with biochemical analyses, provide a better understanding of the signaling mechanism of YycG, which is necessary for developing novel antibacterial drugs targeting S. aureus. Structural Studies on the Extracellular Domain of Sensor Histidine Kinase YycG from Staphylococcus aureus and Its Functional Implications.,Kim T, Choi J, Lee S, Yeo KJ, Cheong HK, Kim KK J Mol Biol. 2016 Jul 4. pii: S0022-2836(16)30241-8. doi:, 10.1016/j.jmb.2016.06.019. PMID:27389096[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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