8T86
Racemic mixture of amylin segment 25-AILSS-29 forms heterochiral rippled beta-sheet
Summary for 8T86
| Entry DOI | 10.2210/pdb8t86/pdb |
| Descriptor | Racemic mixture of amylin segment 25-AILSS-29 (2 entities in total) |
| Functional Keywords | rippled beta sheet, amyloid fibril, protein fibril |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 489.56 |
| Authors | Sawaya, M.R.,Raskatov, J.A.,Hazari, A.,Sajimon, M. (deposition date: 2023-06-21, release date: 2023-11-29, Last modification date: 2023-12-13) |
| Primary citation | Hazari, A.,Sawaya, M.R.,Sajimon, M.,Vlahakis, N.,Rodriguez, J.,Eisenberg, D.,Raskatov, J.A. Racemic Peptides from Amyloid beta and Amylin Form Rippled beta-Sheets Rather Than Pleated beta-Sheets. J.Am.Chem.Soc., 145:25917-25926, 2023 Cited by PubMed Abstract: The rippled β-sheet was theorized by Pauling and Corey in 1953 as a structural motif in which mirror image peptide strands assemble into hydrogen-bonded periodic arrays with strictly alternating chirality. Structural characterization of the rippled β-sheet was limited to biophysical methods until 2022 when atomic resolution structures of the motif were first obtained. The crystal structural foundation is restricted to four model tripeptides composed exclusively of aromatic residues. Here, we report five new rippled sheet crystal structures derived from amyloid β and amylin, the aggregating toxic peptides of Alzheimer's disease and type II diabetes, respectively. Despite the variation in peptide sequence composition, all five structures form antiparallel rippled β-sheets that extend, like a fibril, along the entire length of the crystalline needle. The long-range packing of the crystals, however, varies. In three of the crystals, the sheets pack face-to-face and exclude water, giving rise to cross-β architectures grossly resembling the steric zipper motif of amyloid fibrils but differing in fundamental details. In the other two crystals, the solvent is encapsulated between the sheets, yielding fibril architectures capable of host-guest chemistry. Our study demonstrates that the formation of rippled β-sheets from aggregating racemic peptide mixtures in three-dimensional (3D) assemblies is a general phenomenon and provides a structural basis for targeting intrinsically disordered proteins. PubMed: 37972334DOI: 10.1021/jacs.3c11712 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.102 Å) |
Structure validation
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