Functional characterization of the phosphorelay protein Mpr1p from<i>Schizosaccharomyces pombe</i>

Tan, Hui Yin; Janiak‐Spens, Fabiola; West, Ann H.

doi:10.1111/j.1567-1364.2007.00260.x

Cited by 9 publications

(6 citation statements)

References 24 publications

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“…For example, the extended N-terminal region of the Ypd1 homolog Mpr1 from Sc. pombe has been shown to influence phosphotransfer efficiency between its cognate HHK-binding partner Mak2 by contributing to the protein–protein interaction (Tan, Janiak-Spens and West 2007 ). Thus, diverse functions, such as metal ion binding or stabilization of the phosphoryl group, may allow for specific functions of the N-terminal region and alter the way that the HPt interacts with its binding partners.…”

Section: Resultsmentioning

confidence: 99%

Extended N-terminal region of the essential phosphorelay signaling protein Ypd1 fromCryptococcus neoformanscontributes to structural stability, phosphostability and binding of calcium ions

Kennedy

Menon

West

2016

FEMS Yeast Research

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Rapid response to external stimuli is crucial for survival and proliferation of microorganisms. Pathogenic fungi employ histidine-to-aspartate multistep phosphorelay systems to respond to environmental stress, progress through developmental stages and to produce virulence factors. Because these His-to-Asp phosphorelay systems are not found in humans, they are potential targets for the development of new antifungal therapies. Here we report the characterization of the histidine phosphotransfer (HPt) protein Ypd1 from the human fungal pathogen Cryptococcus neoformans. Results from this study demonstrate that CnYpd1 indeed functions as a phosphorelay protein in vitro, and that H138 is confirmed as the site of phosphorylation. We found that CnYpd1 exhibits unique characteristics in comparison to other histidine phosphotransfer proteins, such as an extended N-terminal amino acid sequence, which we find contributes to structural integrity, a longer phosphorylated life time and the ability to bind calcium ions.

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Section: Resultsmentioning

confidence: 99%

Extended N-terminal region of the essential phosphorelay signaling protein Ypd1 fromCryptococcus neoformanscontributes to structural stability, phosphostability and binding of calcium ions

Kennedy

Menon

West

2016

FEMS Yeast Research

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“…While the HPt domain is highly conserved, a small N-terminal stretch is variable in fungi. Interestingly, the N-terminal extension of Mpr1 is important for the interaction between the HPt and its downstream RR in S. pombe (Tan et al, 2007). …”

Section: Introductionmentioning

confidence: 99%

Fungal Histidine Phosphotransferase Plays a Crucial Role in Photomorphogenesis and Pathogenesis in Magnaporthe oryzae

et al. 2017

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Two-component signal transduction (TCST) pathways play crucial roles in many cellular functions such as stress responses, biofilm formation, and sporulation. The histidine phosphotransferase (HPt), which is an intermediate phosphotransfer protein in a two-component system, transfers a phosphate group to a phosphorylatable aspartate residue in the target protein(s), and up-regulates stress-activated MAP kinase cascades. Most fungal genomes carry a single copy of the gene coding for HPt, which are potential antifungal targets. However, unlike the histidine kinases (HK) or the downstream response regulators (RR) in two-component system, the HPts have not been well-studied in phytopathogenic fungi. In this study, we investigated the role of HPt in the model rice-blast fungal pathogen Magnaporthe oryzae. We found that in M. oryzae an additional isoform of the HPT gene YPD1 was expressed specifically in response to light. Further, the expression of light-regulated genes such as those encoding envoy and blue-light-harvesting protein, and PAS domain containing HKs was significantly reduced upon down-regulation of YPD1 in M. oryzae. Importantly, down-regulation of YPD1 led to a significant decrease in the ability to penetrate the host cuticle and in light-dependent conidiation in M. oryzae. Thus, our results indicate that Ypd1 plays an important role in asexual development and host invasion, and suggest that YPD1 isoforms likely have distinct roles to play in the rice-blast pathogen M. oryzae.

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“…Mak2 and Mak3 have been reported to be involved in signal transduction during oxidative stress, although a mak2,3Δ double mutant strain is not sensitive to hydrogen peroxide (Buck et al 2001). In fission yeast, there is one HPt protein, Mrp1, that functions together with the HKs in response to free radicals (Nguyen et al 2000; Buck et al 2001; Tan et al 2007). The HPt protein transfers the phosphate to one of the two RR proteins named Mcs4 and Prr1 (Buck et al 2001; Quinn et al 2011; Morigasaki and Shiozaki 2013).…”

Section: Introductionmentioning

confidence: 99%

Stress sensitivity of a fission yeast strain lacking histidine kinases is rescued by the ectopic expression of Chk1 from Candida albicans

et al. 2016

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The development of new drugs against the pathogenic yeast Candida albicans is compelling and the evolution of relevant bioassays is important to achieve this goal. Promising drug targets are proteins that lack human counterparts which are true for the His-to-Asp phosphorelay signal transduction systems, important for stress sensing in bacteria, fungi, and plants. In the pathogenic yeast, Candida albicans, the CaChk1 histidine kinase is a trigger of the pathway that leads to a switch from yeast to hyphal growth necessary for invasion. Intriguingly, the model yeast Schizosaccharomyces pombe has a similar phosphorelay system, with three histidine kinases named Mak1, Mak2, and Mak3, which are important for the prevention of aberrant mating and sporulation on rich media. This study uncovered distinct functions for the three histidine kinases; Mak1 alone or Mak2 and Mak3 together were sufficient for the repression of the meiotic cycle when nutrients were available. Moreover, strains lacking histidine kinase genes were sensitive to various types of stress conditions in an auxotrophic strain background, while the stress sensitivity was lost in prototrophic strains. Finally, the stress sensitivity of a S. pombe strain that lacks endogenous histidine kinases could be complemented by the ectopic expression of the CaChk1 histidine kinase from C. albicans. This finding opens up for the possibility to perform a drug screen with a biological read-out in S. pombe to find inhibitors of CaChk1.Electronic supplementary materialThe online version of this article (doi:10.1007/s00294-016-0644-9) contains supplementary material, which is available to authorized users.

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Functional characterization of the phosphorelay protein Mpr1p fromSchizosaccharomyces pombe

Cited by 9 publications

References 24 publications

Extended N-terminal region of the essential phosphorelay signaling protein Ypd1 fromCryptococcus neoformanscontributes to structural stability, phosphostability and binding of calcium ions

Extended N-terminal region of the essential phosphorelay signaling protein Ypd1 fromCryptococcus neoformanscontributes to structural stability, phosphostability and binding of calcium ions

Fungal Histidine Phosphotransferase Plays a Crucial Role in Photomorphogenesis and Pathogenesis in Magnaporthe oryzae

Stress sensitivity of a fission yeast strain lacking histidine kinases is rescued by the ectopic expression of Chk1 from Candida albicans

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