Evolutionary reshaping of fungal mating pathway scaffold proteins.
Scaffold proteins play central roles in the function of many signaling pathways. Among the best-studied examples are the Ste5 and Far1 proteins of the yeast Saccharomyces cerevisiae. These proteins contain three conserved modules, the RING and PH domains, characteristic of some ubiquitin-ligating enzymes, and a vWA domain implicated in protein-protein interactions. In yeast, Ste5p regulates the mating pathway kinases while Far1p coordinates the cellular polarity machinery. Within the fungal lineage, the Basidiomycetes and the Pezizomycetes contain a single Far1-like protein, while several Saccharomycotina species, belonging to the CTG (Candida) clade, contain both a classic Far1-like protein and a Ste5-like protein that lacks the vWA domain. We analyzed the function of C. albicans Ste5p (Cst5p), a member of this class of structurally distinct Ste5 proteins. CST5 is essential for mating and still coordinates the mitogen-activated protein (MAP) kinase (MAPK) cascade elements in the absence of the vWA domain; Cst5p interacts with the MEK kinase (MEKK) C. albicans Ste11p (CaSte11p) and the MAPK Cek1 as well as with the MEK Hst7 in a vWA domain-independent manner. Cst5p can homodimerize, similar to Ste5p, but can also heterodimerize with Far1p, potentially forming heteromeric signaling scaffolds. We found direct binding between the MEKK CaSte11p and the MEK Hst7p that depends on a mobile acidic loop absent from S. cerevisiae Ste11p but related to the Ste7-binding region within the vWA domain of Ste5p. Thus, the fungal lineage has restructured specific scaffolding modules to coordinate the proteins required to direct the gene expression, polarity, and cell cycle regulation essential for mating.
Department of Biology, McGill University, Montreal, Quebec, Canada.
Pierre
P
Côte
Traian
T
Sulea
Daniel
D
Dignard
Cunle
C
Wu
Malcolm
M
Whiteway
D000595:Amino Acid Sequence; D005075:Biological Evolution; D002176:Candida albicans / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005658:Fungi / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D049770:Genes, Mating Type, Fungal; D008969:Molecular Sequence Data; D034521:Nuclear Matrix-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D015398:Signal Transduction
D005656:Fungal Proteins; D034521:Nuclear Matrix-Associated Proteins
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