5VOS
VGSNKGAIIGL from Amyloid Beta determined by MicroED
Summary for 5VOS
| Entry DOI | 10.2210/pdb5vos/pdb |
| Related | 5KNZ |
| EMDB information | 8720 |
| Descriptor | Amyloid beta A4 protein (2 entities in total) |
| Functional Keywords | amyloid, steric zipper, protein fibril |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 1029.21 |
| Authors | Rodriguez, J.A.,Sawaya, M.R.,Cascio, D.,Eisenberg, D.S.,Griner, S.L.,Gonen, T. (deposition date: 2017-05-03, release date: 2018-01-03, Last modification date: 2024-03-13) |
| Primary citation | Krotee, P.,Griner, S.L.,Sawaya, M.R.,Cascio, D.,Rodriguez, J.A.,Shi, D.,Philipp, S.,Murray, K.,Saelices, L.,Lee, J.,Seidler, P.,Glabe, C.G.,Jiang, L.,Gonen, T.,Eisenberg, D.S. Common fibrillar spines of amyloid-beta and human islet amyloid polypeptide revealed by microelectron diffraction and structure-based inhibitors. J. Biol. Chem., 293:2888-2902, 2018 Cited by PubMed Abstract: Amyloid-β (Aβ) 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 Aβ and hIAPP. Using the cryoEM method microelectron diffraction, we determined the atomic structures of 11-residue segments from both Aβ and hIAPP, termed Aβ(24-34) WT and hIAPP(19-29) S20G, with 64% sequence similarity. We observed a high degree of structural similarity between their backbone atoms (0.96-Å root mean square deviation). Moreover, fibrils of these segments induced amyloid formation through self- and cross-seeding. Furthermore, inhibitors designed for one segment showed cross-efficacy for full-length Aβ and hIAPP and reduced cytotoxicity of both proteins, although by apparently blocking different cytotoxic mechanisms. The similarity of the atomic structures of Aβ(24-34) WT and hIAPP(19-29) S20G offers a molecular model for cross-seeding between Aβ and hIAPP. PubMed: 29282295DOI: 10.1074/jbc.M117.806109 PDB entries with the same primary citation |
| Experimental method | ELECTRON CRYSTALLOGRAPHY (1.42 Å) |
Structure validation
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