Essential role of Pro 74 in stefin B amyloid-fibril formation: Dual action of cyclophilin A on the process

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• 作者：Aida Smajlović ; Selma Berbić ; Cordelia Schiene-Fischer ; Magda Tuš ; ek-Ž ; nidarič ; Ajda Taler ; Saš ; a Jenko-Kokalj ; Duš ; an Turk ; Eva Ž ; erovnik
• 关键词：Stefin B ; Amyloid fibril ; Proline cis/trans isomerism ; Cyclophilin A ; Kinetics of fibrillation ; Protein– ; protein interaction
• 刊名：FEBS Letters
• 出版年：2009
• 出版时间：2 April 2009
• 年：2009
• 卷：583
• 期：7
• 页码：1114-1120
• 全文大小：489 K

文摘

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.