Heat shock protein SSA1 and Heat shock protein SSA2 (Ssa1/2)

Heat shock protein SSA1 and SSA2 (Ssa1/2) are essential cytosolic molecular chaperones of the Hsp70 family, primarily characterized in the yeast Saccharomyces cerevisiae and the human pathogen Candida albicans. They function as ATPases that facilitate nascent protein folding, the translocation of polypeptides into the endoplasmic reticulum and mitochondria, and the degradation of misfolded proteins via the ubiquitin-proteasome system. In the cytoplasm, Ssa1/2 also act as negative regulators of the Heat Shock Factor 1 (Hsf1) transcription factor, sequestering it under non-stress conditions. In pathogenic fungi like Candida albicans, these proteins are also localized to the cell surface, where they function as invasins by binding to host E-cadherin to promote fungal entry into epithelial cells. Furthermore, they serve as receptors for salivary antimicrobial peptides such as Histatin 5, mediating their translocation into the fungal cytoplasm. Due to their critical roles in fungal virulence, stress tolerance, and protein homeostasis, Ssa1/2 are considered potential therapeutic targets, though their high homology to human Hsp70 orthologs presents a significant challenge for drug specificity.

Other names

SSA1SSA2Hsp70 family ATPase SSA1Hsp70 family ATPase SSA2Stress-Seventy Subfamily A protein 1Stress-Seventy Subfamily A protein 2YG100

In Candida albicans, Ssa1/2 act as cell-surface receptors for antimicrobial peptides like Histatin 5, facilitating their uptake into the cell where they exert fungicidal effects. Ssa1/2 also function as invasins by binding to host cell cadherins, which triggers fungal endocytosis into host tissues. In the context of stress response, Ssa1/2 negatively regulate Hsf1; chemical modifiers like Celastrol interact with Ssa1 to inhibit its repressor function, thereby activating the heat shock response.