Academic Journal
Polymorphic structures of rapidly twisting 40-residue amyloid-β fibrils.
| Τίτλος: | Polymorphic structures of rapidly twisting 40-residue amyloid-β fibrils. |
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| Συγγραφείς: | Larimi MG; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA., Thurber KR; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA., Tycko R; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA. Electronic address: robertty@mail.nih.gov. |
| Πηγή: | Biophysical journal [Biophys J] 2026 Oct 06; Vol. 125 (19), pp. 5526-5541. Date of Electronic Publication: 2026 Aug 07. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Cell Press Country of Publication: United States NLM ID: 0370626 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1542-0086 (Electronic) Linking ISSN: 00063495 NLM ISO Abbreviation: Biophys J Subsets: MEDLINE |
| Imprint Name(s): | Publication: Cambridge, MA : Cell Press Original Publication: New York, Published by Rockefeller University Press [etc.] for the Biophysical Society. |
| Ιατρικοί όροι (MeSH): | Amyloid beta-Peptides*/chemistry , Peptide Fragments*/chemistry , Amyloid*/chemistry , Protein Multimerization*, Models, Molecular ; Cryoelectron Microscopy ; Protein Conformation |
| Περίληψη: | Fibrils formed by 40- and 42-residue amyloid-β peptides (Aβ40 and Aβ42) are polymorphic, containing molecular structures that vary with growth conditions in ways that are not fully understood. Here, we use cryoelectron microscopy to characterize the structure of rapidly twisting Aβ40 fibrils, for which the distance between apparent width minima in electron microscope images ("cross-over distances") is approximately 25 nm. From samples grown under a single set of growth conditions, we obtain high-resolution structures for three different rapidly twisting polymorphs. Although their cross-over distances are similar, the three rapidly twisting polymorphs differ in twist handedness, symmetry, molecular conformations, and intermolecular contacts. Two of the rapidly twisting polymorphs resemble Aβ40 polymorphs with longer cross-over distances that have been described previously, including polymorphs extracted from brain tissue of patients with Alzheimer's disease or created by seeded growth from amyloid in brain tissue, but have shorter conformationally ordered segments and other specific conformational differences. These results contribute to our understanding of amyloid polymorphism, connections between morphology and molecular structure, and relationships between brain-derived and in-vitro-grown fibrils. (Published by Elsevier Inc.) |
| Competing Interests: | Declaration of interests The authors declare no competing interests. |
| Σχόλια: | Update of: bioRxiv. 2026 Apr 14:2026.04.10.717728. doi: 10.64898/2026.04.10.717728.. (PMID: 42039599) |
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| Grant Information: | Z01 DK029061 United States ImNIH Intramural NIH HHS |
| Substance Nomenclature: | 0 (Amyloid beta-Peptides) 0 (Peptide Fragments) 0 (amyloid beta-protein (1-40)) 0 (Amyloid) |
| Entry Date(s): | Date Created: 20260808 Date Completed: 20261006 Latest Revision: 20261008 |
| Update Code: | 20261008 |
| PubMed Central ID: | PMC13505313 |
| DOI: | 10.1016/j.bpj.2026.08.003 |
| PMID: | 42568185 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1542-0086 |
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| DOI: | 10.1016/j.bpj.2026.08.003 |