Single-point mutation, metal ion concentration and low dielectric constant of the medium induce human ubiquitin aggragation

Ribbon representation of the asymmetric unit content (chains A,B and C) plus one symmetriy-related molecule of chain B (B*), of E16V crystal grown at 35 mM Zn2+. The metal sites (ZN1, Zn5, Zn6 and Zn7) are represented as yellow spheres. The side chain of the mutated residue (Val16) is shown as red sticks

Fermani S et al, Chem. Eur. J., 2017, 24, pp 4140
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Human ubiquitin (hUb) is a small and stable globular protein involved in several aspects of cell physiology. Interest in aggregation pathways of human ubiquitin (hUb) stems from hUb-positive aggregates being biomarkers of neurodegenerative diseases. Two hUb dimers have been recognized as possible precursors of amyloid-like aggregates, but their formation is disfavored by electrostatic repulsions involving mainly Glu16. Substitution of Glu16 negative charge by a metal ion and a decrease of the dielectric constant of the medium can also induce hUb aggregation.
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Aggregation Pathways of Native‐Like Ubiquitin Promoted by Single‐Point Mutation, Metal Ion Concentration, and Dielectric Constant of the Medium;
Fermani S, Calvaresi M, Mangini V, Falini G, Bottoni A, Natile G, Arnesano F, Chem. Eur. J., 2018, 24, pp 4140
DOI: 10.1002/chem.201705543
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