5aef | pdb_00005aef

Electron cryo-microscopy of an Abeta(1-42)amyloid fibril

Loading... Status: waiting for Mol* initialization Structural highlights 5aef is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Alzheimer's disease (AD) is a fatal neurodegenerative disorder in humans and the main cause of dementia in aging societies. The disease is characterized by the aberrant formation of beta-amyloid (Abeta) peptide oligomers and fibrils. These structures may damage the brain and give rise to cerebral amyloid angiopathy, neuronal dysfunction, and cellular toxicity. Although the connection between AD and Abeta fibrillation is extensively documented, much is still unknown about the formation of these Abeta aggregates and their structures at the molecular level. Here, we combined electron cryomicroscopy, 3D reconstruction, and integrative structural modeling methods to determine the molecular architecture of a fibril formed by Abeta(1-42), a particularly pathogenic variant of Abeta peptide. Our model reveals that the individual layers of the Abeta fibril are formed by peptide dimers with face-to-face packing. The two peptides forming the dimer possess identical tilde-shaped conformations and interact with each other by packing of their hydrophobic C-terminal beta-strands. The peptide C termini are located close to the main fibril axis, where they produce a hydrophobic core and are surrounded by the structurally more flexible and charged segments of the peptide N termini. The observed molecular architecture is compatible with the general chemical properties of Abeta peptide and provides a structural basis for various biological observations that illuminate the molecular underpinnings of AD. Moreover, the structure provides direct evidence for a steric zipper within a fibril formed by full-length Abeta peptide. Peptide dimer structure in an Abeta(1-42) fibril visualized with cryo-EM.,Schmidt M, Rohou A, Lasker K, Yadav JK, Schiene-Fischer C, Fandrich M, Grigorieff N Proc Natl Acad Sci U S A. 2015 Sep 22;112(38):11858-63. doi:, 10.1073/pnas.1503455112. Epub 2015 Sep 8. PMID:26351699 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Amyloid precursor protein 3D structures

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