The function of yeast CAP family proteins in lipid export, mating, and pathogen defense

Abstract

In their natural habitat, yeast cells are constantly challenged by changing environmental conditions and a fierce competition for limiting resources. To thrive under such conditions, cells need to adapt and divide quickly, and be able to neutralize the toxic compounds secreted by their neighbors. Proteins like the pathogen‐related yeast, Pry proteins, which belong to the large CAP/SCP/TAPS superfamily, may have an important role in this function. CAP proteins are conserved from yeast to man and are characterized by a unique αβα sandwich fold. They are mostly secreted glycoproteins and have been implicated in many different physiological processes including pathogen defense, virulence, venom toxicity, and sperm maturation. Yeast members of this family bind and export sterols as well as fatty acids, and they render cells resistant to eugenol, an antimicrobial compound present in clove oil. CAP family members might thus exert their various physiological functions through binding, sequestration, and neutralization of such small hydrophobic compounds.

Protein‐facilitated transport of hydrophobic molecules across the yeast plasma membrane

“…However, PRY proteins bind sterols through a separate and independent‐binding site from the hydrophobic tunnel, where they accept free fatty acids (see section on fatty acid efflux) to solubilize the hydrophobic compound and facilitate excretion . Computational modeling studies identify the flexible loop within the CAP domain, which harbors the caveolin‐binding motif (a short stretch of aromatic amino acids) as responsible for sterol binding . This putative mode of sterol binding diverges from what is seen in cytosolic sterol‐binding proteins, such as Osh4, StAR/STARD1, or NPC2, where substrate‐binding site is buried in a hydrophobic tunnel inside the protein.…”

“…Ynl190wp in its role as a hydrophilin, potentially creating a more hydrophilic environment and therefore fortifying the cell wall barrier against organic solvents . In the case of Pry3p, the protective function is an indirect result of its role in yeast mating, which also requires remodeling of the cell wall and fusion of the plasma membranes .…”

“…Computational modeling in comparison to the CAP protein tablysin‐15 suggests substrate binding buried deep inside the protein's hydrophobic channel. The authors stress the mechanistic difference with extracellular fatty acid‐binding proteins (FABP) such as albumins that are believed to bind and solubilize the fatty acids once they are outside the cell .…”

“…Deletion of any one of the PRY genes, including PRY3, resulted in hypersensitivity toward eugenol . Computational modeling and auxiliary competitive assays suggest an overlapping eugenol‐binding site with sterol rather than the free fatty acids, located on the flexible loop of the CAP domain .…”

Cysteine-Rich Secretory Proteins (CRISPs) from Venomous Snakes: An Overview of the Functional Diversity in a Large and Underappreciated Superfamily

“…Sterols are essential for eukaryotes and bacteria, and removing them from membrane surfaces of pathogens inhibits their growth and can even kill them [46]. Lipid-related functions of the CAP superfamily have been summarized by Schneiter et al in two reviews [47,48].…”