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

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 β2-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 fibri

SUBMITTER: Karamanos TK 

PROVIDER: S-EPMC4104025 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature