2LMQ
Structural Model for a 40-residue Beta-Amyloid Fibril with Three-Fold Symmetry, Negative Stagger
Summary for 2LMQ
| Entry DOI | 10.2210/pdb2lmq/pdb |
| Related | 2LMN 2LMO 2LMP |
| NMR Information | BMRB: 18131 |
| Descriptor | Beta-amyloid protein 40 (1 entity in total) |
| Functional Keywords | alzheimer's disease, three-fold symmetry, protein fibril |
| Biological source | Homo sapiens (human) |
| Cellular location | Membrane; Single-pass type I membrane protein: P05067 |
| Total number of polymer chains | 18 |
| Total formula weight | 78045.34 |
| Authors | Tycko, R.,Paravastu, A. (deposition date: 2011-12-09, release date: 2011-12-28, Last modification date: 2024-05-01) |
| Primary citation | Paravastu, A.K.,Leapman, R.D.,Yau, W.M.,Tycko, R. Molecular structural basis for polymorphism in Alzheimer's beta-amyloid fibrils. Proc. Natl. Acad. Sci. U.S.A., 105:18349-18354, 2008 Cited by PubMed Abstract: We describe a full structural model for amyloid fibrils formed by the 40-residue beta-amyloid peptide associated with Alzheimer's disease (Abeta(1-40)), based on numerous constraints from solid state NMR and electron microscopy. This model applies specifically to fibrils with a periodically twisted morphology, with twist period equal to 120 +/- 20 nm (defined as the distance between apparent minima in fibril width in negatively stained transmission electron microscope images). The structure has threefold symmetry about the fibril growth axis, implied by mass-per-length data and the observation of a single set of (13)C NMR signals. Comparison with a previously reported model for Abeta(1-40) fibrils with a qualitatively different, striated ribbon morphology reveals the molecular basis for polymorphism. At the molecular level, the 2 Abeta(1-40) fibril morphologies differ in overall symmetry (twofold vs. threefold), the conformation of non-beta-strand segments, and certain quaternary contacts. Both morphologies contain in-register parallel beta-sheets, constructed from nearly the same beta-strand segments. Because twisted and striated ribbon morphologies are also observed for amyloid fibrils formed by other polypeptides, such as the amylin peptide associated with type 2 diabetes, these structural variations may have general implications. PubMed: 19015532DOI: 10.1073/pnas.0806270105 PDB entries with the same primary citation |
| Experimental method | SOLID-STATE NMR |
Structure validation
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