title: Functional dissection of HAMP domains in NIK1 ortholog from pathogenic yeast Candida lusitaniae.
abstract: Nik1 orthologs or group III hybrid histidine kinases (HHK) are ubiquitous signaling molecules in fungal pathogens. Besides osmosensing, they are also involved in hyphal morphogenesis, virulence, and conidiation. They are important molecular targets for antifungal agents. Nik1 orthologs contain a varying number of HAMP domain repeats (poly-HAMP) in the N-terminal region. Poly-HAMP plays a crucial role in their function. So far, the role of HAMP domains in their function has been studied only in a few Nik1 orthologs. In this paper, we describe the functional characterization of a Nik1 ortholog (ClNik1p) from Candida lusitaniae, an emerging and important fungal pathogen. We show that ClNik1p acts as a bona fide osmosensor and negatively regulates the downstream HOG pathway in Saccharomyces cerevisiae. Our data suggests a differential role of the HAMP domains in the functionality of ClNik1p. The HAMP domains H1, H2, H3 and H5 are essential for kinase activity, and H4 domain has a regulatory role. Among the HAMP like linker domains, only H4b was crucial for the activity of ClNik1p.
authors.affiliation: CSIR - Institute of Microbial Technology, Chandigarh 160036, India.
authors.forename: Anmoldeep
authors.initials: A
authors.lastname: Randhawa
authors.affiliation: CSIR - Institute of Microbial Technology, Chandigarh 160036, India.
authors.forename: Srishti
authors.initials: S
authors.lastname: Chawla
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India. Electronic address: akmondal@mail.jnu.ac.in.
authors.forename: Alok K
authors.initials: AK
authors.lastname: Mondal
mesh_terms: D002175:Candida / Q000201:enzymology / Q000235:genetics*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D064587:Osmoregulation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D005656:Fungal Proteins; D017346:Protein Serine-Threonine Kinases
keywords: Candida lusitaniae; Fungi; Group III hybrid histidine kinase; HAMP domain; Nik1; Osmosensor