Refine
Has Fulltext
- yes (5)
Is part of the Bibliography
- yes (5)
Document Type
- Journal article (4)
- Doctoral Thesis (1)
Language
- English (5)
Keywords
- Candida albicans (4)
- cell wall (2)
- protein kinases (2)
- AMP-activated kinases (1)
- Mig1 (1)
- SNF1 (1)
- Snf1 (1)
- candida (1)
- candida albicans (1)
- conditional mutants (1)
- essential genes (1)
- fungus (1)
- genetic recombination (1)
- kinase (1)
- metabolic adaptation (1)
- protein kinase (1)
- signaling pathway (1)
- suppressor mutation (1)
- yeast (1)
- zinc cluster transcription factor (1)
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.