Title |
Zinc-binding domain mediates pleiotropic functions of Yvh1 in Cryptococcus neoformans |
Author |
Jae-Hyung Jin1, Myung Kyung Choi2, Hyun-Soo Cho2, and Yong-Sun Bahn1* |
Address |
1Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea, 2Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea |
Bibliography |
Journal of Microbiology, 59(7),658–665, 2021,
|
DOI |
10.1007/s12275-021-1287-1
|
Key Words |
DUSP, fungal meningoencephalitis, zinc finger,
virulence |
Abstract |
Yvh1 is a dual-specificity phosphatase (DUSP) that is evolutionarily
conserved in eukaryotes, including yeasts and humans.
Yvh1 is involved in the vegetative growth, differentiation,
and virulence of animal and plant fungal pathogens.
All Yvh1 orthologs have a conserved DUSP catalytic domain
at the N-terminus and a zinc-binding (ZB) domain with two
zinc fingers (ZFs) at the C-terminus. Although the DUSP domain
is implicated in the regulation of MAPK signaling in
humans, only the ZB domain is essential for most cellular
functions of Yvh1 in fungi. This study aimed to analyze the
functions of the DUSP and ZB domains of Yvh1 in the human
fungal pathogen Cryptococcus neoformans, whose Yvh1
(CnYvh1) contains a DUSP domain at the C-terminus and
a ZB domain at the N-terminus. Notably, CnYvh1 has an extended
internal domain between the two ZF motifs in the ZB
domain. To elucidate the function of each domain, we constructed
individual domain deletions and swapping strains
by complementing the yvh1Δ mutant with wild-type (WT)
or mutated YVH1 alleles and examined their Yvh1-dependent
phenotypes, including growth under varying stress conditions,
mating, and virulence factor production. Here, we found
that the complementation of the yvh1Δ mutant with the mutated
YVH1 alleles having two ZFs of the ZB domain, but not
the DUSP and extended internal domains, restored the WT
phenotypic traits in the yvh1Δ mutant. In conclusion, the
ZB domain, but not the N-terminal DUSP domain, plays a
pivotal role in the pathobiological functions of cryptococcal
Yvh1. |