Abstract
For several different proteins an apparent correlation has been observed between the propensity for dimerization by domain-swapping and the ability to aggregate into amyloid-like fibrils. Examples include the disease-related proteins β 2-microglobulin and transthyretin. This has led to proposals that the amyloid-formation pathway may feature extensive domain swapping. One possible consequence of such an aggregation pathway is that the resulting fibrils would incorporate structural elements that resemble the domain-swapped forms of the protein and, thus, reflect certain native-like structures or domain-interactions. In magic angle spinning solid-state NMR-based and other structural studies of such amyloid fibrils, it appears that many of these proteins form fibrils that are not native-like. Several fibrils, instead, have an in-register, parallel conformation, which is a common amyloid structural motif and is seen, for instance, in various prion fibrils. Such a lack of native structure in the fibrils suggests that the apparent connection between domain-swapping ability and amyloid-formation may be more subtle or complex than may be presumed at first glance.
Original language | English |
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Pages (from-to) | 211-6 |
Number of pages | 6 |
Journal | Prion |
Volume | 6 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1-Jul-2012 |
Externally published | Yes |
Keywords
- Amyloid/chemistry
- Animals
- Humans
- Models, Molecular
- Nuclear Magnetic Resonance, Biomolecular
- Protein Conformation
- Protein Multimerization
- Protein Structure, Tertiary
- beta 2-Microglobulin/chemistry
- HUMAN CYSTATIN-C
- SOLID-STATE NMR
- HUMAN PRION PROTEIN
- ANGLE-SPINNING NMR
- NATIVE-LIKE
- BETA-STRANDS
- CRYSTAL-STRUCTURE
- TRANSTHYRETIN
- DIMER
- BETA-2-MICROGLOBULIN