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Intragenic suppressor mutations of the COQ8 protein kinase homolog restore coenzyme Q biosynthesis and function in Saccharomyces cerevisiae.
PLoS One. 2020; 15(6):e0234192.Plos

Abstract

Saccharomyces cerevisiae Coq8 is a member of the ancient UbiB atypical protein kinase family. Coq8, and its orthologs UbiB, ABC1, ADCK3, and ADCK4, are required for the biosynthesis of coenzyme Q in yeast, E. coli, A. thaliana, and humans. Each Coq8 ortholog retains nine highly conserved protein kinase-like motifs, yet its functional role in coenzyme Q biosynthesis remains mysterious. Coq8 may function as an ATPase whose activity is stimulated by coenzyme Q intermediates and phospholipids. A key yeast point mutant expressing Coq8-A197V was previously shown to result in a coenzyme Q-less, respiratory deficient phenotype. The A197V substitution occurs in the crucial Ala-rich protein kinase-like motif I of yeast Coq8. Here we show that long-term cultures of mutants expressing Coq8-A197V produce spontaneous revertants with the ability to grow on medium containing a non-fermentable carbon source. Each revertant is shown to harbor a secondary intragenic suppressor mutation within the COQ8 gene. The intragenic suppressors restore the synthesis of coenzyme Q. One class of the suppressors fully restores the levels of coenzyme Q and key Coq polypeptides necessary for the maintenance and integrity of the high-molecular mass CoQ synthome (also termed complex Q), while the other class provides only a partial rescue. Mutants harboring the first class of suppressors grow robustly under respiratory conditions, while mutants containing the second class grow more slowly under these conditions. Our work provides insight into the function of this important yet still enigmatic Coq8 family.

Authors+Show Affiliations

Department of Chemistry and Biochemistry, and the Molecular Biology Institute, University of California, Los Angeles, California, United States of America.Department of Chemistry and Biochemistry, and the Molecular Biology Institute, University of California, Los Angeles, California, United States of America.Department of Chemistry and Biochemistry, and the Molecular Biology Institute, University of California, Los Angeles, California, United States of America.Department of Chemistry and Biochemistry, and the Molecular Biology Institute, University of California, Los Angeles, California, United States of America.Department of Chemistry and Biochemistry, and the Molecular Biology Institute, University of California, Los Angeles, California, United States of America.Department of Chemistry and Biochemistry, and the Molecular Biology Institute, University of California, Los Angeles, California, United States of America.Department of Chemistry and Biochemistry, and the Molecular Biology Institute, University of California, Los Angeles, California, United States of America.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32479562

Citation

Awad, Agape M., et al. "Intragenic Suppressor Mutations of the COQ8 Protein Kinase Homolog Restore Coenzyme Q Biosynthesis and Function in Saccharomyces Cerevisiae." PloS One, vol. 15, no. 6, 2020, pp. e0234192.
Awad AM, Nag A, Pham NVB, et al. Intragenic suppressor mutations of the COQ8 protein kinase homolog restore coenzyme Q biosynthesis and function in Saccharomyces cerevisiae. PLoS ONE. 2020;15(6):e0234192.
Awad, A. M., Nag, A., Pham, N. V. B., Bradley, M. C., Jabassini, N., Nathaniel, J., & Clarke, C. F. (2020). Intragenic suppressor mutations of the COQ8 protein kinase homolog restore coenzyme Q biosynthesis and function in Saccharomyces cerevisiae. PloS One, 15(6), e0234192. https://doi.org/10.1371/journal.pone.0234192
Awad AM, et al. Intragenic Suppressor Mutations of the COQ8 Protein Kinase Homolog Restore Coenzyme Q Biosynthesis and Function in Saccharomyces Cerevisiae. PLoS ONE. 2020;15(6):e0234192. PubMed PMID: 32479562.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intragenic suppressor mutations of the COQ8 protein kinase homolog restore coenzyme Q biosynthesis and function in Saccharomyces cerevisiae. AU - Awad,Agape M, AU - Nag,Anish, AU - Pham,Nguyen V B, AU - Bradley,Michelle C, AU - Jabassini,Nour, AU - Nathaniel,Juan, AU - Clarke,Catherine F, Y1 - 2020/06/01/ PY - 2019/11/17/received PY - 2020/05/20/accepted PY - 2020/6/2/entrez PY - 2020/6/2/pubmed PY - 2020/6/2/medline SP - e0234192 EP - e0234192 JF - PloS one JO - PLoS ONE VL - 15 IS - 6 N2 - Saccharomyces cerevisiae Coq8 is a member of the ancient UbiB atypical protein kinase family. Coq8, and its orthologs UbiB, ABC1, ADCK3, and ADCK4, are required for the biosynthesis of coenzyme Q in yeast, E. coli, A. thaliana, and humans. Each Coq8 ortholog retains nine highly conserved protein kinase-like motifs, yet its functional role in coenzyme Q biosynthesis remains mysterious. Coq8 may function as an ATPase whose activity is stimulated by coenzyme Q intermediates and phospholipids. A key yeast point mutant expressing Coq8-A197V was previously shown to result in a coenzyme Q-less, respiratory deficient phenotype. The A197V substitution occurs in the crucial Ala-rich protein kinase-like motif I of yeast Coq8. Here we show that long-term cultures of mutants expressing Coq8-A197V produce spontaneous revertants with the ability to grow on medium containing a non-fermentable carbon source. Each revertant is shown to harbor a secondary intragenic suppressor mutation within the COQ8 gene. The intragenic suppressors restore the synthesis of coenzyme Q. One class of the suppressors fully restores the levels of coenzyme Q and key Coq polypeptides necessary for the maintenance and integrity of the high-molecular mass CoQ synthome (also termed complex Q), while the other class provides only a partial rescue. Mutants harboring the first class of suppressors grow robustly under respiratory conditions, while mutants containing the second class grow more slowly under these conditions. Our work provides insight into the function of this important yet still enigmatic Coq8 family. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/32479562/Intragenic_suppressor_mutations_of_the_COQ8_protein_kinase_homolog_restore_coenzyme_Q_biosynthesis_and_function_in_Saccharomyces_cerevisiae L2 - https://dx.plos.org/10.1371/journal.pone.0234192 DB - PRIME DP - Unbound Medicine ER -
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