7Y8Q

Amyloid-beta assemblage on GM1-containing membranes

Summary for 7Y8Q

• Entry DOI: 10.2210/pdb7y8q/pdb
• Descriptor: Amyloid-beta protein 40 (1 entity in total)
• Functional Keywords: amyloid, alzheimer's disease, assemblage, membrane, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 8
• Total formula weight: 34686.82

Authors

Yagi-Utsumi, M.,Itoh, S.G.,Okumura, H.,Yanagisawa, K.,Kato, K.,Nishimura, K. (deposition date: 2022-06-24, release date: 2023-07-05, Last modification date: 2024-05-15)

Primary citation

Yagi-Utsumi, M.,Itoh, S.G.,Okumura, H.,Yanagisawa, K.,Kato, K.,Nishimura, K.
The Double-Layered Structure of Amyloid-beta Assemblage on GM1-Containing Membranes Catalytically Promotes Fibrillization.
Acs Chem Neurosci, 14:2648-2657, 2023

PubMed Abstract: Alzheimer's disease (AD) is associated with progressive accumulation of amyloid-β (Aβ) cross-β fibrils in the brain. Aβ species tightly associated with GM1 ganglioside, a glycosphingolipid abundant in neuronal membranes, promote amyloid fibril formation; therefore, they could be attractive clinical targets. However, the active conformational state of Aβ in GM1-containing lipid membranes is still unknown. The present solid-state nuclear magnetic resonance study revealed a nonfibrillar Aβ assemblage characterized by a double-layered antiparallel β-structure specifically formed on GM1 ganglioside clusters. Our data show that this unique assemblage was not transformed into fibrils on GM1-containing membranes but could promote conversion of monomeric Aβ into fibrils, suggesting that a solvent-exposed hydrophobic layer provides a catalytic surface evoking Aβ fibril formation. Our findings offer structural clues for designing drugs targeting catalytically active Aβ conformational species for the development of anti-AD therapeutics.

PubMed: 37482658
DOI: 10.1021/acschemneuro.3c00192

Experimental method

SOLID-STATE NMR