3QO5

Crystal Structure of the seryl-tRNA synthetase from Candida albicans

Summary for 3QO5

• Entry DOI: 10.2210/pdb3qo5/pdb
• Related: 3QNE 3QO7 3QO8
• Descriptor: Seryl-tRNA synthetase, cytoplasmic (2 entities in total)
• Functional Keywords: genetic code ambiguity, trna, class-ii aminoacyl-trna synthetase family, type-1 seryl-trna synthetase subfamily, trna aminoacylation, serine, ligase
• Biological source: Candida albicans (yeast)
• Cellular location: Cytoplasm: Q9HGT6
• Total number of polymer chains: 1
• Total formula weight: 55708.95

Authors

Rocha, R.,Santos, M.A.,Pereira, P.J.B.,Macedo-Ribeiro, S. (deposition date: 2011-02-09, release date: 2011-08-03, Last modification date: 2023-09-13)

Primary citation

Rocha, R.,Pereira, P.J.,Santos, M.A.,Macedo-Ribeiro, S.
Unveiling the structural basis for translational ambiguity tolerance in a human fungal pathogen.
Proc.Natl.Acad.Sci.USA, 108:14091-14096, 2011

PubMed 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.

PubMed: 21825144
DOI: 10.1073/pnas.1102835108

Experimental method

X-RAY DIFFRACTION (2.3 Å)