title: Aggregation mechanisms of cystatins: a comparative study of monellin and oryzacystatin.
abstract: Identification of diseases caused by protein misfolding has increased interest in the way proteins adopt non-native conformations and form aggregates. In this study we address the question of how proteins sharing the same fold respond to destabilizing environmental conditions. We have studied the behavior of two members of the cystatin superfamily, MNEI, a single chain monellin, and oryzacystatin_I, a plant cystatin. Despite the close similarity of their three-dimensional architecture, these two proteins aggregate in a different way: MNEI gives rise to amyloid aggregation whereas oryzacystatin_I yields amorphous aggregates. Mutants of oryzacystatin_I, designed to make it more similar to MNEI, generally behave like the parent protein, but a construct devoid of the disordered N- and C-terminal sequences does show a tendency to form amyloid fibers. Our results suggest that precise sequence details may be more important than the three-dimensional architecture in determining the type of aggregate formed. Oryzacystatin_I appears to be a very promising model system for further studies of protein aggregation.
authors.affiliation: MRC National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK.
authors.forename: Veronica
authors.initials: V
authors.lastname: Esposito
authors.forename: Fulvio
authors.initials: F
authors.lastname: Guglielmi
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Martin
authors.forename: Kris
authors.initials: K
authors.lastname: Pauwels
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pastore
authors.forename: Renata
authors.initials: R
authors.lastname: Piccoli
authors.forename: Piero A
authors.initials: PA
authors.lastname: Temussi
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid; D015891:Cystatins / Q000737:chemistry*; D012275:Oryza / Q000737:chemistry; D010940:Plant Proteins / Q000737:chemistry*; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D055503:Protein Multimerization
chemical_list: D000682:Amyloid; D015891:Cystatins; D010940:Plant Proteins