Journal
MOLECULAR CELL
Volume 55, Issue 2, Pages 214-226Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2014.05.026
Keywords
-
Categories
Funding
- Wellcome Trust [094232, 089311/Z/09/Z]
- University of Leeds
- European Research Council (ERC) under European Union/ERC [322408]
- Wellcome Trust [089311/Z/09/Z] Funding Source: Wellcome Trust
Ask authors/readers for more resources
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 beta(2)-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available