title: Governing the monomer-dimer ratio of human cystatin c by single amino acid substitution in the hinge region.
abstract: Three dimensional domain swapping is one of the mechanisms involved in formation of insoluble aggregates of some amyloidogenic proteins. It has been proposed that proteins able to swap domains may share some common structural elements like conformationally constrained flexible turns/loops. We studied the role of loop L1 in the dimerization of human cystatin C using mutational analysis. Introduction of turn-favoring residues such as Asp or Asn into the loop sequence (in position 57) leads to a significant reduction of the dimer fraction in comparison with the wild type protein. On the other hand, introduction of a proline residue in position 57 leads to efficient dimer formation. Our results confirm the important role of the loop L1 in the dimerization process of human cystatin C and show that this process can be to some extent governed by single amino acid substitution.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Chemistry, University of Gdańsk, J. Sobieskiego 18, Gdańsk, Poland. aneta@chem.univ.gda.pl
authors.forename: Aneta
authors.initials: A
authors.lastname: Szymańska
authors.forename: Adrianna
authors.initials: A
authors.lastname: Radulska
authors.forename: Paulina
authors.initials: P
authors.lastname: Czaplewska
authors.forename: Anders
authors.initials: A
authors.lastname: Grubb
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Grzonka
authors.forename: Sylwia
authors.initials: S
authors.lastname: Rodziewicz-Motowidło
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology*; D002850:Chromatography, Gel; D002942:Circular Dichroism; D055316:Cystatin C / Q000737:chemistry* / Q000235:genetics; D004586:Electrophoresis; D006801:Humans; D016297:Mutagenesis, Site-Directed; D055503:Protein Multimerization / Q000235:genetics / Q000502:physiology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D055316:Cystatin C