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Essential role of Pro 74 in stefin B amyloid‐fibril formation: Dual action of cyclophilin A on the process
Author(s) -
Smajlović Aida,
Berbić Selma,
Schiene-Fischer Cordelia,
Tušek-Žnidarič Magda,
Taler Ajda,
Jenko-Kokalj Saša,
Turk Dušan,
Žerovnik Eva
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.02.037
Subject(s) - prolyl isomerase , fibril , chemistry , cyclophilin , peptidylprolyl isomerase , mutant , cis trans isomerases , isomerization , amyloid fibril , biophysics , isomerase , cyclophilin a , yield (engineering) , amyloid (mycology) , pin1 , biochemistry , biology , amyloid β , enzyme , materials science , microbiology and biotechnology , medicine , inorganic chemistry , disease , pathology , metallurgy , gene , catalysis
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 °C, and it exhibited a prolonged lag phase at 30 °C and 37 °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.