Analysis of heterologous expression of Candida albicans SEC61 gene reveals differences in Sec61p homologues related to species-specific functionality.

Abstract

The protein secretory pathway has not been studied in depth in Candida albicans despite its essential role in the secretion of enzymes and cell surface components related to the ability of the fungus to colonize the human host. To gain further insight into the elements that participate in the first stages of the secretory process in this fungal pathogen we have isolated and characterized the C. albicans ortholog of SEC61. In other species SEC61 has been shown to encode the core element of the protein translocation apparatus within the ER membrane. The cloned gene appears to be essential for cell viability and encodes a highly conserved protein, very similar to the Sec61p from other yeast species both in sequence and hydropathy profile. However, CaSec61p is not able to complement the thermosensitive-growth phenotype of a Saccharomyces cerevisiae sec61 mutant, even though it is expressed and correctly incorporated into the ER membrane of the transformant cells. We report results indicating that the lack of functional complementation could be related to differences in the primary structure of the cytosolic domain located between the fourth and fifth transmembrane domains of the accepted topological model of Sec61p.