9M5Q

V-type (V1-type) amyloid fibril (40) of Tottori (D7N) mutant

This is a non-PDB format compatible entry.

Summary for 9M5Q

• Entry DOI: 10.2210/pdb9m5q/pdb
• EMDB information: 63647
• Descriptor: Amyloid-beta protein 40 (1 entity in total)
• Functional Keywords: amyloid, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 21
• Total formula weight: 91032.21

Authors

Burton-Smith, R.N.,Murata, K. (deposition date: 2025-03-06, release date: 2025-07-09)

Primary citation

Yagi-Utsumi, M.,Yanaka, S.,Burton-Smith, R.N.,Song, C.,Ganser, C.,Yamazaki, C.,Kasahara, H.,Shimazu, T.,Uchihashi, T.,Murata, K.,Kato, K.
Microgravity-Assisted Exploration of the Conformational Space of Amyloid beta Affected by Tottori-Type Familial Mutation D7N.
Acs Chem Neurosci, 2025

PubMed Abstract: The amyloid β (Aβ) Tottori variant (D7N) exhibits unique aggregation behaviors and altered fibril formation, posing challenges for structural characterization. To overcome this, the microgravity environment on the International Space Station was employed to study Tottori-type Aβ40 fibril formation and structure. Under Earth gravity, Tottori-type Aβ40 primarily formed nonfibrillar aggregates, hindering detailed structural analysis. In contrast, microgravity significantly enhanced fibril formation and minimized amorphous aggregates. Cryo-electron microscopy revealed two structurally distinct fibril types, each comprising different protomer conformations. In both types, the N-terminal segment was disordered and nor resolved in the density maps. The D7N mutation disrupts the protection of the core by the N-terminal segment often observed in wild-type Aβ40 fibrils, enhancing the hydrophobicity-mediated aggregation propensity. However, microgravity suppressed kinetic traps and facilitated high-quality fibril formation suitable for structural studies that can explore the free energy landscape of Aβ fibril formation. These findings demonstrate the utility of microgravity for studying familial Aβ variants and potentially accelerate our understanding of Aβ aggregation mechanisms in Alzheimer's disease.

PubMed: 40554613
DOI: 10.1021/acschemneuro.5c00217

Experimental method

ELECTRON MICROSCOPY (3.3 Å)