title: The sixth HAMP domain negatively regulates the activity of the group III HHK containing seven HAMP domains.
abstract: In fungi, the group III hybrid histidine kinases (HHK) act as important sensors to regulate osmoadaptation, hyphal growth, morphogenesis, conidia formation and virulence. They are molecular targets for antifungal agent fludioxonil. They typically have HAMP domain repeats at the NH2-terminus that are important for their activity. Interestingly, the numbers of HAMP domain vary among the orthologs from different genera. The orthologs from basidiomycetes harbor seven HAMP domains whereas those from yeast contain five HAMP domains. In order to understand the functioning of a seven-HAMP module, we have constructed a yeast-like chimera DhNik1-Tco1 containing seven HAMP domains. The functional characterization of this chimera in yeast Saccharomyces cerevisiae showed that the sixth HAMP domain played important regulatory role. Our results indicated that the negative regulation of histidine kinase activity by the penultimate HAMP domain could possibly be an evolutionarily conserved theme in the group III HHK containing different lengths of poly HAMP module.
authors.affiliation: CSIR-Institute of Microbial Technology, Sector 39A, Chandigarh 160 036, India.
authors.forename: Anmoldeep
authors.initials: A
authors.lastname: Randhawa
authors.forename: Alok K
authors.initials: AK
authors.lastname: Mondal
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004149:Dioxoles / Q000494:pharmacology*; D000071677:Histidine Kinase; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011758:Pyrroles / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D004149:Dioxoles; D011758:Pyrroles; D011494:Protein Kinases; D000071677:Histidine Kinase; C108339:fludioxonil
keywords: Fludioxonil; Fungi; HAMP domain; HOG pathway; Hybrid histidine kinase