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http://hdl.handle.net/10773/27913
Title: | Unveiling the structural basis for translational ambiguity tolerance in a human fungal pathogen |
Author: | Rocha, Rita Pereira, Pedro José Barbosa Santos, Manuel A. S. Macedo-Ribeiro, Sandra |
Keywords: | Aminoacyl-tRNA synthetase Morphogenesis Mitogen-activated protein kinase Pathway Ras1X-ray crystallography |
Issue Date: | 23-Aug-2011 |
Publisher: | National Academy of Sciences |
Abstract: | In a restricted group of opportunistic fungal pathogens the universal leucine CUG codon is translated both as serine (97%) and leucine (3%), challenging the concept that translational ambiguity has a negative impact in living organisms. To elucidate the molecular mechanisms underlying the in vivo tolerance to a nonconserved genetic code alteration, we have undertaken an extensive structural analysis of proteins containing CUG-encoded residues and solved the crystal structures of the two natural isoforms of Candida albicans seryl-tRNA synthetase. We show that codon reassignment resulted in a nonrandom genome-wide CUG redistribution tailored to minimize protein misfolding events induced by the large-scale leucine-to-serine replacement within the CTG clade. Leucine or serine incorporation at the CUG position in C. albicans seryl-tRNA synthetase induces only local structural changes and, although both isoforms display tRNA serylation activity, the leucine-containing isoform is more active. Similarly, codon ambiguity is predicted to shape the function of C. albicans proteins containing CUG-encoded residues in functionally relevant positions, some of which have a key role in signaling cascades associated with morphological changes and pathogenesis. This study provides a first detailed analysis on natural reassignment of codon identity, unveiling a highly dynamic evolutionary pattern of thousands of fungal CUG codons to confer an optimized balance between protein structural robustness and functional plasticity. |
Peer review: | yes |
URI: | http://hdl.handle.net/10773/27913 |
DOI: | 10.1073/pnas.1102835108 |
ISSN: | 0027-8424 |
Appears in Collections: | CESAM - Artigos DBio - Artigos |
Files in This Item:
File | Description | Size | Format | |
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Rocha et al. - 2011 - Unveiling the structural basis for translational a.pdf | 1.37 MB | Adobe PDF | View/Open |
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