6VU4
Structure of a beta-hairpin peptide mimic derived from Abeta 14-36
Summary for 6VU4
| Entry DOI | 10.2210/pdb6vu4/pdb |
| Descriptor | Beta-hairpin Amyloid-beta precursor peptide mimic, IODIDE ION, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | alzheimer's disease, neuropeptide |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 4154.10 |
| Authors | Wierzbicki, M.,Kreutzer, A.,Samdin, T.,Nowick, J.S. (deposition date: 2020-02-14, release date: 2020-06-17, Last modification date: 2023-10-11) |
| Primary citation | Samdin, T.D.,Wierzbicki, M.,Kreutzer, A.G.,Howitz, W.J.,Valenzuela, M.,Smith, A.,Sahrai, V.,Truex, N.L.,Klun, M.,Nowick, J.S. Effects of N-Terminal Residues on the Assembly of Constrained beta-Hairpin Peptides Derived from A beta. J.Am.Chem.Soc., 142:11593-11601, 2020 Cited by PubMed Abstract: This paper describes the synthesis, solution-phase biophysical studies, and X-ray crystallographic structures of hexamers formed by macrocyclic β-hairpin peptides derived from the central and C-terminal regions of Aβ, which bear "tails" derived from the N-terminus of Aβ. Soluble oligomers of the β-amyloid peptide, Aβ, are thought to be the synaptotoxic species responsible for neurodegeneration in Alzheimer's disease. Over the last 20 years, evidence has accumulated that implicates the N-terminus of Aβ as a region that may initiate the formation of damaging oligomeric species. We previously studied, in our laboratory, macrocyclic β-hairpin peptides derived from Aβ and Aβ, capable of forming hexamers that can be observed by X-ray crystallography and SDS-PAGE. To better mimic oligomers of full length Aβ, we use an orthogonal protecting group strategy during the synthesis to append residues from Aβ to the parent macrocyclic β-hairpin peptide , which comprises Aβ and Aβ. The N-terminally extended peptides , , , , , , , and assemble to form dimers, trimers, and hexamers in solution-phase studies. X-ray crystallography reveals that peptide assembles to form a hexamer that is composed of dimers and trimers. These observations are consistent with a model in which the assembly of Aβ oligomers is driven by hydrogen bonding and hydrophobic packing of the residues from the central and C-terminal regions, with the N-terminus of Aβ accommodated by the oligomers as an unstructured tail. PubMed: 32501687DOI: 10.1021/jacs.0c05186 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.077 Å) |
Structure validation
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