title: Essential role of Pro 74 in stefin B amyloid-fibril formation: dual action of cyclophilin A on the process.
abstract: We report that Pro74 in human stefin B is critical for fibril formation and that proline isomerization plays an important role. The stefin B P74S mutant did not fibrillate over the time of observation at 25 degrees C, and it exhibited a prolonged lag phase at 30 degrees C and 37 degrees C. The peptidyl prolyl cis/trans isomerase cyclophilin A, when added to the wild-type protein, exerted two effects: it prolonged the lag phase and increased the yield and length of the fibrils. Addition of the inactive cyclophilin A R55A variant still resulted in a prolonged lag phase but did not mediate the increase of the final fibril yield. These results demonstrate that peptidyl prolyl cis/trans isomerism is rate-limiting in stefin B fibril formation.
authors.affiliation: Department of Biochemistry, Farmaceutical Faculty, University of Tuzla, Tuzla, Bosnia and Herzegovina.
authors.forename: Aida
authors.initials: A
authors.lastname: Smajlović
authors.forename: Selma
authors.initials: S
authors.lastname: Berbić
authors.forename: Cordelia
authors.initials: C
authors.lastname: Schiene-Fischer
authors.forename: Magda
authors.initials: M
authors.lastname: Tusek-Znidaric
authors.forename: Ajda
authors.initials: A
authors.lastname: Taler
authors.forename: Sasa
authors.initials: S
authors.lastname: Jenko-Kokalj
authors.forename: Dusan
authors.initials: D
authors.lastname: Turk
authors.forename: Eva
authors.initials: E
authors.lastname: Zerovnik
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D021984:Cyclophilin A / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D055313:Cystatin B / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D011392:Proline / Q000235:genetics / Q000378:metabolism; D020836:Protein Structure, Quaternary / Q000235:genetics; D013997:Time Factors
chemical_list: D000682:Amyloid; C524994:CSTB protein, human; D055313:Cystatin B; D011392:Proline; D021984:Cyclophilin A