Ser or Leu - Functional and Structural impact of ambiguous translation in Candida albicans
Speaker: Sandra de Macedo Ribeiro
Instituto de Biologia Molecular e Celular - IBMC [Porto Portugal]
Host: José María de Pereda
Salón de Actos del Centro de Investigación del Cáncer
Candida albicans, an opportunistic fungal pathogen, accounts for nearly 400,000 life-threatening infections per year (mortality rate >30%) and many more mucosal infections. The most relevant virulence factor of C. albicans is its morphological plasticity: yeast to hypha interchange is essential for blood propagation, tissue invasion and immune evasion. This transition is controlled by a complex netowrk of signalling pathways activated by external stimuli, which trigger the appropriate adaptive responses. Interestingly, C. albicans has genetic code ambiguity, wherein CTG, an otherwise Leu encoding codon, codes for Ser (97%) or Leu (3%). This is particularly important as the level of leucine incorporation increases during stress. Accumulating evidence suggests that C. albicans is perfectly adapted this translational ambiguity and CTG encoded residues are generally located in regions that are not expected to significantly interfere with protein structure and function. However, our studies revealed that in a small subset of key signalling proteins involved in adaptation CTG-residues are located in conserved regions, close to active centres or macromolecular recognition sites (Rocha et al. PNAS 2011). The talk will focus on the recent results from the group showing that Ser or Leu insertion at CTG positions modifies the stability and activity of signalling kinases that are critical for cell wall remodelling and host-pathogen interactions.