7ROJ

Amyloid-related segment of alphaB-crystallin residues 90-100 with G95W mutation

Summary for 7ROJ

• Entry DOI: 10.2210/pdb7roj/pdb
• Descriptor: Alpha-crystallin B chain peptide, SODIUM ION, trifluoroacetic acid, ... (5 entities in total)
• Functional Keywords: amyloid oligomer, protein fibril
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 12
• Total formula weight: 16526.68

Authors

Sawaya, M.R.,Do, T.D.,Eisenberg, D.S. (deposition date: 2021-07-30, release date: 2022-01-12, Last modification date: 2023-10-18)

Primary citation

Gray, A.L.H.,Sawaya, M.R.,Acharyya, D.,Lou, J.,Edington, E.M.,Best, M.D.,Prosser, R.A.,Eisenberg, D.S.,Do, T.D.
Atomic view of an amyloid dodecamer exhibiting selective cellular toxic vulnerability in acute brain slices.
Protein Sci., 31:716-727, 2022

PubMed Abstract: Atomic structures of amyloid oligomers that capture the neurodegenerative disease pathology are essential to understand disease-state causes and finding cures. Here we investigate the G6W mutation of the cytotoxic, hexameric amyloid model KV11. The mutation results into an asymmetric dodecamer composed of a pair of 30° twisted antiparallel β-sheets. The complete break between adjacent β-strands is unprecedented among amyloid fibril crystal structures and supports that our structure is an oligomer. The poor shape complementarity between mated sheets reveals an interior channel for binding lipids, suggesting that the toxicity may be due to a perturbation of lipid transport rather than a direct disruption of membrane integrity. Viability assays on mouse suprachiasmatic nucleus, anterior hypothalamus, and cerebral cortex demonstrated selective regional vulnerability consistent with Alzheimer's disease. Neuropeptides released from the brain slices may provide clues to how G6W initiates cellular injury.

PubMed: 34954854
DOI: 10.1002/pro.4268

Experimental method

X-RAY DIFFRACTION (1.6 Å)