Fungal yapsins and cell wall: a unique family of aspartic peptidases for a distinctive cellular function

Abstract

A novel class of aspartic peptidases known as fungal yapsins, whose first member ScYps1p was identified more than a decade ago in Saccharomyces cerevisiae, is characteristically modified by the addition of a glycophosphatidylinositol moiety and has a preference for cleaving substrates C-terminally to mono- and paired-basic residues. Over the years, several other members, first in S. cerevisiae and then in other fungi, have been identified. The implication of fungal yapsins in cell-wall assembly and/or remodelling had been suspected for many years. However, it is only very recently that studies performed on S. cerevisae and Candida albicans have confirmed their importance for cell-wall integrity. Here, we review 16 years of research, covering all fundamental aspects of these unique enzymes, in an effort to track their functional significance. We also propose a nomenclature for fungal yapsins based on their sequence identity with the founding members of this family, the S. cerevisiae yapsins.

Proteolytic Cleavage of Covalently Linked Cell Wall Proteins by Candida albicans Sap9 and Sap10

“…Cutfield et al (13) have determined residues in the Sap2 sequence which are involved in pepstatin A binding. Strikingly, two of these amino acids differ in both Sap9 and Sap10 compared to Sap2 (I 86 A systematic screen of synthetic peptides for Sap9 and Sap10 cleavage confirmed our previous observation that both proteases prefer cleavage at basic lysine or arginine or dibasic residues, similar to S. cerevisiae yapsins (1,21). However, both Sap9 and Sap10 cleavage events also occurred independent of basic residues, an ability that seems to be specific for the C. albicans yapsin-like proteases.…”

“…Both proteases are, like other Sap family members, targeted to the cellular secretion machinery by an Nterminal signal peptide. However, only Sap9 and Sap10 contain C-terminal GPI consensus sequences, which mediate localization in the cell membrane and cell wall (1), a feature typical for members of the Saccharomyces cerevisiae yapsin family of regulatory aspartic proteases (21). In agreement with such regulatory functions, mutants lacking SAP9 or SAP10 exhibit profound cell wall and cell separation defects and are modified in their interaction with epithelial cells and neutrophils (1,26).…”

Multistep processing of the secretion leader of the extracellular protein Epx1 in Pichia pastoris and implications for protein localization

“…The first amino acids of the mature Epx1 protein are similar to the sequence of S. cerevisiae MFa, which is subject to the cleavage by Bar1 (Ballensiefen & Schmitt, 1997), while yapsins are described to recognize and cleave mainly at monobasic residues (reviewed by Gagnon-Arsenault et al, 2006). Homologues of Bar1, as well as seven members of the yapsin family, can be found in the P. pastoris genome.…”

Candida albicansCell Wall Proteins

“…During this decade, there have been multiple reviews on various aspects of the C. albicans cell surface, including several very recently (100,101,116,187,215,246,312,322,355,381). The proteins of the cell wall may play a role in maintaining structural integrity and in mediating adherence, whether to host or microbes, or they may have enzymatic functions, e.g., proteolysis.…”