Coq3p relevant residues for protein activity and stability

Author(s)

Paulela, Janaina A. ; Gomes, Fernando ; Camandona, Vittoria de Lima ; Alegria, Thiago G. P. ; Netto, Luis E. S. ; Bleicher, Lucas ; Barros, Mario H. ; Ferreira-Junior, Jose Ribamar

• Document type: Journal article
• Source: FEMS Yeast Research; v. 21, n. 7, p. 16-pg., 2021-11-01.

Abstract

Coenzyme Q (CoQ) is an essential molecule that consists of a highly substituted benzene ring attached to a polyprenyl tail anchored in the inner mitochondrial membrane. CoQ transfers electrons from NADH dehydrogenase and succinate dehydrogenase complexes toward ubiquinol-cytochrome c reductase, and that allows aerobic growth of cells. In Saccharomyces cerevisiae, the synthesis of CoQ depends on fourteen proteins Coq1p-Co11p, Yah1p, Arh1p, and Hfd1p. Some of these proteins are components of CoQ synthome. Using ab initio molecular modeling and site-directed mutagenesis, we identified the functional residues of the 0-methyltransferase Coq3p, which depends on S-adenosylmethionine for catalysis and is necessary for two O-methylation steps required for CoQ maturation. Conserved residues as well as those that coevolved in the protein structure were found to have important roles in respiratory growth, CoQ biosynthesis, and also in the stability of CoQ synthome proteins. Finally, a multiple sequence alignment showed that S. cerevisiae Coq3p has a 45 amino acid residues insertion that is poorly conserved or absent in oleaginous yeast, cells that can store up to 20% of their dry weight as lipids. These results point to the Coq3p structural determinants of its biological and catalytic function and could contribute to the development of lipid-producing yeast for biotechnology. (AU)

• FAPESP's process: 17/09443-3 - Importing of peroxiredoxins to distinct mitochondrial compartments: impacts on physiology and pathology
• Grantee: Fernando Gomes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/00586-5 - Structural mapping of Rtg2p determinants involved in retrograde signaling and aging of Saccharomyces cerevisiae
• Grantee: José Ribamar dos Santos Ferreira Júnior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC