title: Proline Residues as Switches in Conformational Changes Leading to Amyloid Fibril Formation.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia. ajda.taler@ijs.si.|CIPKeBiP-Center of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Jamova 39, 1000 Ljubljana, Slovenia. ajda.taler@ijs.si.
authors.forename: Ajda
authors.initials: A
authors.lastname: Taler-Verčič
authors.affiliation: Jožef Stefan International Postgraduate School, Jamova 39, 1000 Ljubljana, Slovenia. samra1988@hotmail.com.|Faculty of Pharmacy, Department of Biochemistry, University of Tuzla, Univerzitetska 1, 75000 Tuzla, Bosnia and Herzegovina. samra1988@hotmail.com.
authors.forename: Samra
authors.initials: S
authors.lastname: Hasanbašić
authors.affiliation: Faculty of Pharmacy, Department of Biochemistry, University of Tuzla, Univerzitetska 1, 75000 Tuzla, Bosnia and Herzegovina. selma.berbic@untz.ba.
authors.forename: Selma
authors.initials: S
authors.lastname: Berbić
authors.affiliation: Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia. veronika.stoka@ijs.si.|Jožef Stefan International Postgraduate School, Jamova 39, 1000 Ljubljana, Slovenia. veronika.stoka@ijs.si.
authors.forename: Veronika
authors.initials: V
authors.lastname: Stoka
authors.affiliation: Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia. dusan.turk@ijs.si.|CIPKeBiP-Center of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Jamova 39, 1000 Ljubljana, Slovenia. dusan.turk@ijs.si.|Jožef Stefan International Postgraduate School, Jamova 39, 1000 Ljubljana, Slovenia. dusan.turk@ijs.si.
authors.forename: Dušan
authors.initials: D
authors.lastname: Turk
authors.affiliation: Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia. eva.zerovnik@ijs.si.|CIPKeBiP-Center of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Jamova 39, 1000 Ljubljana, Slovenia. eva.zerovnik@ijs.si.|Jožef Stefan International Postgraduate School, Jamova 39, 1000 Ljubljana, Slovenia. eva.zerovnik@ijs.si.
authors.forename: Eva
authors.initials: E
authors.lastname: Žerovnik
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D055313:Cystatin B / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D051379:Mice; D008958:Models, Molecular; D009154:Mutation; D011392:Proline / Q000737:chemistry* / Q000235:genetics; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological; D011487:Protein Conformation; D017510:Protein Folding; D055503:Protein Multimerization; D055550:Protein Stability; D001613:beta 2-Microglobulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D000682:Amyloid; D066329:Protein Aggregates; D001613:beta 2-Microglobulin; D055313:Cystatin B; D011392:Proline
keywords: amyloid fibrils; cis proline; conformational switch; domain swapping; folding intermediate; protein aggregation; stefin B; β2-microglobulin