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Distinct role of HAMP and HAMP-like linker domains in regulating the activity of Hik1p, a hybrid histidine kinase 3 from Magnaporthe oryzae

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Abstract

Nik1 orthologs or group III hybrid histidine kinases (HHK3) represent a unique cytoplasmic osmosensor that act upstream of HOG/p38 MAPK pathway in fungi. It is an important molecular target for developing new antifungal agents against human pathogens. HHK3 orthologs contain a linear array of alternative HAMP and HAMP-like linker domains (poly-HAMP) in the N-terminal region. HAMP domains are quite common in prokaryotic histidine kinases where it mostly functions as signal transducer mediating conformational changes in the kinase domains. In contrast, poly-HAMP in HHK3 acts as a sensor and signal transducer to regulate histidine kinase activity. However, the mechanistic detail of this is poorly understood. Interestingly, recent studies indicate that the poly-HAMP-mediated regulation of the kinase activity varies among the orthologs. Hik1 is an important HHK3 ortholog from fungus Magnaporthe oryzae. In this paper, we aimed to decipher the role HAMP and HAMP-like linker domains in regulating the activity of Hik1p. We show that Hik1p acts as a bona fide osmosensor and negatively regulates the downstream HOG/p38 MAPK pathway in Saccharomyces cerevisiae. Our data suggest a differential role of the HAMP domains in the functionality of Hik1p. Most interestingly, the deletion of individual domains in poly-HAMP resulted in distinct active forms of Hik1p and thereby indicating that the poly-HAMP domain, instead of acting as on–off switch, regulates the histidine kinase activity by transition through multiple conformational states.

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Abbreviations

HHK:

Hybrid histidine kinase

aa:

Amino acid

bp:

Base pair

Kb:

Kilo base

β-gal:

β-Galactosidase

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Acknowledgements

Plasmid pYES-HIK1 is a kind gift from Takayuki Motoyama, RIKEN (The Institute of Physical and Chemical Research), Wako City, Japan. Work is supported by grant no CRG/2020/002107 from Department of Science and Technology (IN) to AKM. HK, SPS, AY and YM are recipients of CSIR-UGC Senior research fellowship.

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Authors and Affiliations

  1. CSIR-Institute of Microbial Technology, Sector 39A, Chandigarh, India

    Harsimran Kaur & Alok K. Mondal

  2. School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India

    Soorya Partap Sasan, Anita Yadav, Yogita Martoliya & Alok K. Mondal

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  1. Harsimran Kaur
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  2. Soorya Partap Sasan
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  3. Anita Yadav
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  4. Yogita Martoliya
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  5. Alok K. Mondal
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Contributions

HR—investigation; formal analysis; writing—original draft; SPS—validation; investigation; visualization; writing—review and editing. AY—validation; visualization; writing—review and editing. YM—validation; visualization; writing—review and editing. AKM—conceptualization; supervision; project administration; funding acquisition; writing—review and editing.

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Correspondence to Alok K. Mondal.

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Communicated by Stefan Hohmann.

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438_2021_1809_MOESM1_ESM.tif

Supplementary file1 Growth pattern of S. cerevisiae strain AMY1000 transformed with Hik1 or different mutant in the presence doxycycline or fludioxonil. Tenfold serial dilutions of overnight cultures were spotted on minimal SD plates without leucine, with doxycycline (10 µg/ml) or with fludioxonil (50 µg/ml) and plates were incubated at 28 ºC for 3 days. Growth on doxycycline plate indicates that Hik1 or its mutant complements Sln1 function in S. cerevisiae. Absence of growth in fludioxonil plate indicates HIK1 or its mutant confers fludioxonil sensitivity to host. A, B—Individual and serially deleted HAMP domain mutants. C, D—HAMP-like linker domain mutants

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Kaur, H., Sasan, S.P., Yadav, A. et al. Distinct role of HAMP and HAMP-like linker domains in regulating the activity of Hik1p, a hybrid histidine kinase 3 from Magnaporthe oryzae. Mol Genet Genomics 296, 1135–1145 (2021). https://doi.org/10.1007/s00438-021-01809-7

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