TY  - JOUR
A1  - Mottola, Austin
A1  - Morschhäuser, Joachim
T1  - An intragenic recombination event generates a Snf4-independent form of the essential protein kinase SNF1 in Candida albicans
T2  - mSphere
N2  - The heterotrimeric protein kinase SNF1 plays a key role in the metabolic adaptation of the pathogenic yeast Candida albicans. It consists of the essential catalytic α-subunit Snf1, the γ-subunit Snf4, and one of the two β-subunits Kis1 and Kis2. Snf4 is required to release the N-terminal catalytic domain of Snf1 from autoinhibition by the C-terminal regulatory domain, and snf4Δ mutants cannot grow on carbon sources other than glucose. In a screen for suppressor mutations that restore growth of a snf4Δ mutant on alternative carbon sources, we isolated a mutant in which six amino acids between the N-terminal kinase domain and the C-terminal regulatory domain of Snf1 were deleted. The deletion was caused by an intragenic recombination event between two 8-bp direct repeats flanking six intervening codons. In contrast to truncated forms of Snf1 that contain only the kinase domain, the Snf4-independent Snf1\(^{Δ311 − 316}\) was fully functional and could replace wild-type Snf1 for normal growth, because it retained the ability to interact with the Kis1 and Kis2 β-subunits via its C-terminal domain. Indeed, the Snf4-independent Snf1\(^{Δ311 − 316}\) still required the β-subunits of the SNF1 complex to perform its functions and did not rescue the growth defects of kis1Δ mutants. Our results demonstrate that a preprogrammed in-frame deletion event within the SNF1 coding region can generate a mutated form of this essential kinase which abolishes autoinhibition and thereby overcomes growth deficiencies caused by a defect in the γ-subunit Snf4.
KW  - AMP-activated kinases
KW  - Candida albicans
KW  - genetic recombination
KW  - metabolic adaptation
KW  - suppressor mutation
Y1  - 2019
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/20217
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-202170
VL  - 4
IS  - 3
ER  -