5SUT
X-ray crystallographic structure of a covalent trimer derived from A-beta 17_36. Synchrotron data set. (ORN)CVFFCED(ORN)AII(SAR)L(ORN)V.
Summary for 5SUT
Entry DOI | 10.2210/pdb5sut/pdb |
Related | 5SUR 5SUS 5SUU |
Descriptor | 16mer A-beta peptide: ORN-CYS-VAL-PHE-PHE-CYS-GLU-ASP-ORN-ALA-ILE-ILE-SAR-LEU-ORN-VAL, CHLORIDE ION (3 entities in total) |
Functional Keywords | amyloid, oligomer, alzheimer's, trimer, protein fibril, de novo protein |
Biological source | Homo sapiens |
Total number of polymer chains | 2 |
Total formula weight | 3605.81 |
Authors | Kreutzer, A.G.,Spencer, R.K.,Nowick, J.S. (deposition date: 2016-08-03, release date: 2017-01-11, Last modification date: 2024-03-27) |
Primary citation | Kreutzer, A.G.,Yoo, S.,Spencer, R.K.,Nowick, J.S. Stabilization, Assembly, and Toxicity of Trimers Derived from A beta. J.Am.Chem.Soc., 139:966-975, 2017 Cited by PubMed Abstract: Oligomers of the β-amyloid peptide Aβ have emerged as important contributors to neurodegeneration in Alzheimer's disease. Mounting evidence suggests that Aβ trimers and higher-order oligomers derived from trimers have special significance in the early stages of Alzheimer's disease. Elucidating the structures of these trimers and higher-order oligomers is paramount for understanding their role in neurodegeneration. This paper describes the design, synthesis, X-ray crystallographic structures, and biophysical and biological properties of two stabilized trimers derived from the central and C-terminal regions of Aβ. These triangular trimers are stabilized through three disulfide cross-links between the monomer subunits. The X-ray crystallographic structures reveal that the stabilized trimers assemble hierarchically to form hexamers, dodecamers, and annular porelike structures. Solution-phase biophysical studies reveal that the stabilized trimers assemble in solution to form oligomers that recapitulate some of the higher-order assemblies observed crystallographically. The stabilized trimers share many of the biological characteristics of oligomers of full-length Aβ, including toxicity toward a neuronally derived human cell line, activation of caspase-3 mediated apoptosis, and reactivity with the oligomer-specific antibody A11. These studies support the biological significance of the triangular trimer assembly of Aβ β-hairpins and may offer a deeper understanding of the molecular basis of Alzheimer's disease. PubMed: 28001392DOI: 10.1021/jacs.6b11748 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.902 Å) |
Structure validation
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