Structural and functional study of YER067W, a new protein involved in yeast metabolism control and drug resistance
| Autor: | João Claudio Gonçalves Freire, Eleonora Kurtenbach, Claudio A. Masuda, Tatiana Domitrovic, Kalle Gehring, Marcius S. Almeida, Edna Matta-Camacho, Guennadi Kozlov, Georgia C. Atella, Mónica Montero-Lomelí |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Antifungal Agents
Protein Conformation Computational Biology/Macromolecular Structure Analysis Computational Biology/Comparative Sequence Analysis chemistry.chemical_compound Protein structure Peptide sequence Fluconazole Phylogeny 2. Zero hunger 0303 health sciences Ergosterol Multidisciplinary Drug Resistance Microbial Biochemistry/Molecular Evolution Transmembrane domain Biochemistry Biochemistry/Bioinformatics Medicine Research Article Saccharomyces cerevisiae Proteins Protein family Science Cell Biology/Microbial Physiology and Metabolism Saccharomyces cerevisiae Genes Fungal Molecular Sequence Data Computational Biology/Transcriptional Regulation Biology 03 medical and health sciences Cell Biology/Microbial Growth and Development Amphotericin B Amino Acid Sequence Gene Cell Biology/Chemical Biology of the Cell Cell Biology/Gene Expression 030304 developmental biology Sequence Homology Amino Acid 030306 microbiology Biochemistry/Structural Genomics Biochemistry/Chemical Biology of the Cell Membrane Proteins Biophysics/Structural Genomics Computational Biology/Macromolecular Sequence Analysis biology.organism_classification Yeast Carbon Computational Biology/Bio-ontology chemistry Energy Metabolism |
| Zdroj: | PLoS ONE PLoS ONE, Vol 5, Iss 6, p e11163 (2010) |
| ISSN: | 1932-6203 |
| Popis: | The genome of Saccharomyces cerevisiae is arguably the best studied eukaryotic genome, and yet, it contains approximately 1000 genes that are still relatively uncharacterized. As the majority of these ORFs have no homologs with characterized sequence or protein structure, traditional sequence-based approaches cannot be applied to deduce their biological function. Here, we characterize YER067W, a conserved gene of unknown function that is strongly induced in response to many stress conditions and repressed in drug resistant yeast strains. Gene expression patterns of YER067W and its paralog YIL057C suggest an involvement in energy metabolism. We show that yeast lacking YER067W display altered levels of reserve carbohydrates and a growth deficiency in media that requires aerobic metabolism. Impaired mitochondrial function and overall reduction of ergosterol content in the YER067W deleted strain explained the observed 2- and 4-fold increase in resistance to the drugs fluconazole and amphotericin B, respectively. Cell fractionation and immunofluorescence microscopy revealed that Yer067w is associated with cellular membranes despite the absence of a transmembrane domain in the protein. Finally, the 1.7 A resolution crystal structure of Yer067w shows an alpha-beta fold with low similarity to known structures and a putative functional site. YER067W's involvement with aerobic energetic metabolism suggests the assignment of the gene name RGI1, standing for respiratory growth induced 1. Altogether, the results shed light on a previously uncharacterized protein family and provide basis for further studies of its apparent role in energy metabolism control and drug resistance. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|