2NAO

Atomic resolution structure of a disease-relevant Abeta(1-42) amyloid fibril

Summary for 2NAO

• Entry DOI: 10.2210/pdb2nao/pdb
• NMR Information: BMRB: 26692
• Descriptor: Beta-amyloid protein 42 (1 entity in total)
• Functional Keywords: protein fibril
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P05067
• Total number of polymer chains: 6
• Total formula weight: 27120.52

Authors

Waelti, M.A.,Ravotti, F.,Arai, H.,Glabe, C.,Wall, J.,Bockmann, A.,Guntert, P.,Meier, B.H.,Riek, R. (deposition date: 2016-01-07, release date: 2016-07-27, Last modification date: 2024-05-01)

Primary citation

Walti, M.A.,Ravotti, F.,Arai, H.,Glabe, C.G.,Wall, J.S.,Bockmann, A.,Guntert, P.,Meier, B.H.,Riek, R.
Atomic-resolution structure of a disease-relevant A beta (1-42) amyloid fibril.
Proc.Natl.Acad.Sci.USA, 113:E4976-E4984, 2016

PubMed Abstract: Amyloid-β (Aβ) is present in humans as a 39- to 42-amino acid residue metabolic product of the amyloid precursor protein. Although the two predominant forms, Aβ(1-40) and Aβ(1-42), differ in only two residues, they display different biophysical, biological, and clinical behavior. Aβ(1-42) is the more neurotoxic species, aggregates much faster, and dominates in senile plaque of Alzheimer's disease (AD) patients. Although small Aβ oligomers are believed to be the neurotoxic species, Aβ amyloid fibrils are, because of their presence in plaques, a pathological hallmark of AD and appear to play an important role in disease progression through cell-to-cell transmissibility. Here, we solved the 3D structure of a disease-relevant Aβ(1-42) fibril polymorph, combining data from solid-state NMR spectroscopy and mass-per-length measurements from EM. The 3D structure is composed of two molecules per fibril layer, with residues 15-42 forming a double-horseshoe-like cross-β-sheet entity with maximally buried hydrophobic side chains. Residues 1-14 are partially ordered and in a β-strand conformation, but do not display unambiguous distance restraints to the remainder of the core structure.

PubMed: 27469165
DOI: 10.1073/pnas.1600749113

Experimental method

SOLUTION NMR