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http://hdl.handle.net/10773/27913
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DC Field | Value | Language |
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dc.contributor.author | Rocha, Rita | pt_PT |
dc.contributor.author | Pereira, Pedro José Barbosa | pt_PT |
dc.contributor.author | Santos, Manuel A. S. | pt_PT |
dc.contributor.author | Macedo-Ribeiro, Sandra | pt_PT |
dc.date.accessioned | 2020-03-12T12:22:13Z | - |
dc.date.available | 2020-03-12T12:22:13Z | - |
dc.date.issued | 2011-08-23 | - |
dc.identifier.issn | 0027-8424 | pt_PT |
dc.identifier.uri | http://hdl.handle.net/10773/27913 | - |
dc.description.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. | pt_PT |
dc.language.iso | eng | pt_PT |
dc.publisher | National Academy of Sciences | pt_PT |
dc.relation | info:eu-repo/grantAgreement/FCT/5876-PPCDTI/70634/PT | pt_PT |
dc.relation | info:eu-repo/grantAgreement/FCT/5876-PPCDTI/64745/PT | pt_PT |
dc.relation | PTDC/SAUGMG/098850/2008 | pt_PT |
dc.relation | info:eu-repo/grantAgreement/FCT/5876-PPCDTI/99826/PT | pt_PT |
dc.relation | REEQ/564/BIO/2005 | pt_PT |
dc.relation | info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F15233%2F2004/PT | pt_PT |
dc.rights | openAccess | pt_PT |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | pt_PT |
dc.subject | Aminoacyl-tRNA synthetase | pt_PT |
dc.subject | Morphogenesis | pt_PT |
dc.subject | Mitogen-activated protein kinase | pt_PT |
dc.subject | Pathway | pt_PT |
dc.subject | Ras1X-ray crystallography | pt_PT |
dc.title | Unveiling the structural basis for translational ambiguity tolerance in a human fungal pathogen | pt_PT |
dc.type | article | pt_PT |
dc.description.version | published | pt_PT |
dc.peerreviewed | yes | pt_PT |
degois.publication.firstPage | 14091 | pt_PT |
degois.publication.issue | 34 | pt_PT |
degois.publication.lastPage | 14096 | pt_PT |
degois.publication.title | Proceedings of the National Academy of Sciences | pt_PT |
degois.publication.volume | 108 | pt_PT |
dc.identifier.doi | 10.1073/pnas.1102835108 | pt_PT |
dc.identifier.essn | 1091-6490 | pt_PT |
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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