Visualization of Transient Protein-Protein Interactions that Promote or Inhibit Amyloid Assembly
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, ou...
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| Format: | Online |
| Language: | English |
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Cell Press
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104025/ |
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pubmed-4104025 |
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pubmed-41040252014-07-24 Visualization of Transient Protein-Protein Interactions that Promote or Inhibit Amyloid Assembly Karamanos, Theodoros K. Kalverda, Arnout P. Thompson, Gary S. Radford, Sheena E. Article 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 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. Cell Press 2014-07-17 /pmc/articles/PMC4104025/ /pubmed/24981172 http://dx.doi.org/10.1016/j.molcel.2014.05.026 Text en © 2014 The Authors http://creativecommons.org/licenses/by/3.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Karamanos, Theodoros K. Kalverda, Arnout P. Thompson, Gary S. Radford, Sheena E. |
| spellingShingle |
Karamanos, Theodoros K. Kalverda, Arnout P. Thompson, Gary S. Radford, Sheena E. Visualization of Transient Protein-Protein Interactions that Promote or Inhibit Amyloid Assembly |
| author_facet |
Karamanos, Theodoros K. Kalverda, Arnout P. Thompson, Gary S. Radford, Sheena E. |
| author_sort |
Karamanos, Theodoros K. |
| title |
Visualization of Transient Protein-Protein Interactions that Promote or Inhibit Amyloid Assembly |
| title_short |
Visualization of Transient Protein-Protein Interactions that Promote or Inhibit Amyloid Assembly |
| title_full |
Visualization of Transient Protein-Protein Interactions that Promote or Inhibit Amyloid Assembly |
| title_fullStr |
Visualization of Transient Protein-Protein Interactions that Promote or Inhibit Amyloid Assembly |
| title_full_unstemmed |
Visualization of Transient Protein-Protein Interactions that Promote or Inhibit Amyloid Assembly |
| title_sort |
visualization of transient protein-protein interactions that promote or inhibit amyloid assembly |
| description |
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 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. |
| publisher |
Cell Press |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104025/ |
| _version_ |
1613115874783264768 |