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An intragenic recombination event generates a Snf4-independent form of the essential protein kinase SNF1 in Candida albicans
Please always quote using this URN: urn:nbn:de:bvb:20-opus-202170
- 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, weThe 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.…
Author: | Austin Mottola, Joachim Morschhäuser |
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URN: | urn:nbn:de:bvb:20-opus-202170 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Institut für Molekulare Infektionsbiologie |
Language: | English |
Parent Title (English): | mSphere |
Year of Completion: | 2019 |
Volume: | 4 |
Issue: | 3 |
Pagenumber: | e00352-19 |
Source: | mSphere (2019) 4:3, e00352-19. https://doi.org/10.1128/mSphere.00352-19 |
DOI: | https://doi.org/10.1128/mSphere.00352-19 |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Tag: | AMP-activated kinases; Candida albicans; genetic recombination; metabolic adaptation; suppressor mutation |
Release Date: | 2020/05/14 |
Collections: | Open-Access-Publikationsfonds / Förderzeitraum 2019 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |