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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 DOI10.2210/pdb5sut/pdb
Related5SUR 5SUS 5SUU
Descriptor16mer 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 Keywordsamyloid, oligomer, alzheimer's, trimer, protein fibril, de novo protein
Biological sourceHomo sapiens
Total number of polymer chains2
Total formula weight3605.81
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 citationKreutzer, 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: 28001392
DOI: 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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