Visualization of transient protein-protein interactions that promote or inhibit amyloid assembly

Karamanos, TK and Kalverda, AP and Thompson, GS and Radford, SE (2014) Visualization of transient protein-protein interactions that promote or inhibit amyloid assembly. Molecular Cell, 55 . pp. 214-226. ISSN 1097-2765. (doi:https://doi.org/10.1016/j.molcel.2014.05.026) (Full text available)

Abstract

In the early stages of amyloid formation, heterogeneous populations of oligomeric species are generated, the affinity, specificity, and nature of which may promote, inhibit, or define the course of assembly. Despite the importance of the intermolecular interactions that initiate amyloid assembly, our understanding of these events remains poor. Here, using amyloidogenic and nonamyloidogenic variants of ?-microglobulin, we identify the interactions that inhibit or promote fibril formation in atomic detail. The results reveal that different outcomes of assembly result from biomolecular interactions involving similar surfaces. Specifically, inhibition occurs via rigid body docking of monomers in a head-to-head orientation to form kinetically trapped dimers. By contrast, the promotion of fibrillation involves relatively weak protein association in a similar orientation, which results in conformational changes in the initially nonfibrillogenic partner. The results highlight the complexity of interactions early in amyloid assembly and reveal atomic-level information about species barriers in amyloid formation.

Item Type: Article
Subjects: Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: G. Thompson
Date Deposited: 23 Jan 2019 21:23 UTC
Last Modified: 24 Jan 2019 11:55 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/71802 (The current URI for this page, for reference purposes)
Thompson, GS: https://orcid.org/0000-0001-9399-7636
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