Proline Residues as Switches in Conformational Changes Leading to Amyloid Fibril Formation

• Main Authors: Ajda Taler-Verčič, Samra Hasanbašić, Selma Berbić, Veronika Stoka, Dušan Turk, Eva Žerovnik
• Format: Article
• Language: English
• Published: MDPI AG 2017-03-01
• Series: International Journal of Molecular Sciences
• Subjects: cis proline; conformational switch; folding intermediate; domain swapping; amyloid fibrils; protein aggregation; stefin B; β2-microglobulin
• Online Access: http://www.mdpi.com/1422-0067/18/3/549

Here we discuss studies of the structure, folding, oligomerization and amyloid fibril formation of several proline mutants of human stefin B, which is a protein inhibitor of lysosomal cysteine cathepsins and a member of the cystatin family. The structurally important prolines in stefin B are responsible for the slow folding phases and facilitate domain swapping (Pro 74) and loop swapping (Pro 79). Moreover, our findings are compared to β2-microglobulin, a protein involved in dialysis-related amyloidosis. The assessment of the contribution of proline residues to the process of amyloid fibril formation may shed new light on the critical molecular events involved in conformational disorders.