title: Hsp90-Associated Immunophilin Homolog Cpr7 Is Required for the Mitotic Stability of [URE3] Prion in Saccharomyces cerevisiae.
abstract: The role of Hsp70 chaperones in yeast prion propagation is well established. Highly conserved Hsp90 chaperones participate in a number of cellular processes, such as client protein maturation, protein degradation, cellular signalling and apoptosis, but little is known about their role in propagation of infectious prion like aggregates. Here, we examine the influence of Hsp90 in the maintenance of yeast prion [URE3] which is a prion form of native protein Ure2, and reveal a previously unknown role of Hsp90 as an important regulator of [URE3] stability. We show that the C-terminal MEEVD pentapeptide motif, but not the client maturation activity of Hsp90, is essential for [URE3] prion stability. In testing deletions of various Hsp90 co-chaperones known to bind this motif, we find the immunophilin homolog Cpr7 is essential for [URE3] propagation. We show that Cpr7 interacts with Ure2 and enhances its fibrillation. The requirement of Cpr7 is specific for [URE3] as its deletion does not antagonize both strong and weak variant of another yeast prion [PSI+], suggesting a distinct role of the Hsp90 co-chaperone with different yeast prions. Our data show that, similar to the Hsp70 family, the Hsp90 chaperones also influence yeast prion maintenance, and that immunophilins could regulate protein multimerization independently of their activity as peptidyl-prolyl isomerases.
authors.affiliation: Council of Scientific and Industrial Research-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Navinder
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Council of Scientific and Industrial Research-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Deepika
authors.initials: D
authors.lastname: Gaur
authors.affiliation: Council of Scientific and Industrial Research-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Arpit
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Council of Scientific and Industrial Research-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Anuradhika
authors.initials: A
authors.lastname: Puri
authors.affiliation: Council of Scientific and Industrial Research-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Sharma
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000235:genetics*; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D008938:Mitosis / Q000235:genetics; D018832:Molecular Chaperones / Q000235:genetics; D011328:Prions / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D000097322:Peptidyl-Prolyl Isomerase D
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins; D005979:Glutathione Peroxidase; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins; C000631445:CPR7 protein, S cerevisiae; D000097322:Peptidyl-Prolyl Isomerase D; C074510:HSP82 protein, S cerevisiae; C067020:URE2 protein, S cerevisiae