5vos

VGSNKGAIIGL from Amyloid Beta determined by MicroED

spinqualitylabelsall models 5vos, resolution 1.42Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5vos is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 5knz Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Amyloid-beta (Abeta) and human islet amyloid polypeptide (hIAPP) aggregate to form amyloid fibrils that deposit in tissues, and are associated with Alzheimer's disease (AD) and Type-II Diabetes (T2D), respectively. Individuals with T2D have an increased risk of developing AD, and conversely, AD patients have an increased risk of developing T2D. Evidence suggests that this link between AD and T2D might originate from a structural similarity between aggregates of Abeta and hIAPP. Using the cryoEM method Micro-Electron Diffraction (MicroED) we determined the atomic structures of 11-residue segments from both Abeta and hIAPP, termed Abeta 24-34 WT and hIAPP 19-29 S20G, with 64% sequence similarity. We observe a high degree of structural similarity between their backbone atoms (0.96 A RMSD). Moreover, fibrils of these segments induce amyloid formation through self- and cross-seeding. Furthermore, inhibitors designed for one segment show cross-efficacy for full-length Abeta and hIAPP and reduce cytotoxicity of both proteins, though by apparently blocking different cytotoxic mechanisms. The similarity of the atomic structures of Abeta 24-34 WT and hIAPP 19-29 S20G offers a molecular model for cross-seeding between Abeta and hIAPP. Common fibrillar spines of amyloid-beta and human Islet Amyloid Polypeptide revealed by Micro Electron Diffraction and inhibitors developed using structure-based design.,Krotee P, Griner SL, Sawaya MR, Cascio D, Rodriguez JA, Shi D, Philipp S, Murray K, Saelices L, Lee J, Seidler P, Glabe CG, Jiang L, Gonen T, Eisenberg DS J Biol Chem. 2017 Dec 27. pii: M117.806109. doi: 10.1074/jbc.M117.806109. PMID:29282295 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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