Time-resolved small-angle X-ray scattering study of polymorphic nature of Aß42 oligomerisation

Tia Cheremnykh.

SASDPU7 – Amyloid Beta 1-42 (cluster 1, Set 1, initial state)

Amyloid-beta precursor protein
MWexperimental 26 kDa
MWexpected 5 kDa
log I(s) 1.52×10-2 1.52×10-3 1.52×10-4 1.52×10-5
Amyloid-beta precursor protein small angle scattering data  s, nm-1
ln I(s)
Amyloid-beta precursor protein Guinier plot ln 1.52×10-2 Rg: 3.5 nm 0 (3.5 nm)-2 s2
(sRg)2I(s)/I(0)
Amyloid-beta precursor protein Kratky plot 1.104 0 √3 sRg
p(r)
Amyloid-beta precursor protein pair distance distribution function Rg: 4.1 nm 0 Dmax: 15 nm

Data validation

Fits and models

log I(s)
 s, nm-1
Amyloid-beta precursor protein DAMMIN model
Synchrotron SAXS data from solutions of Amyloid Beta 1-42 (cluster 1, Set 1, initial state) in 1 mM Hepes, 0.12 % NH4OH, pH 10.7 were collected on the EMBL P12 beam line at the PETRA III storage ring (DESY; Hamburg, Germany) using a Pilatus 6M detector at a sample-detector distance of 3.1 m and at a wavelength of λ = 0.124 nm (I(s) vs s, where s = 4πsinθ/λ, and 2θ is the scattering angle). One solute concentration of 2.00 mg/ml was measured at 20°C. 100 successive 0.045 second frames were collected. The data were normalized to the intensity of the transmitted beam and radially averaged; the scattering of the solvent-blank was subtracted.

SAXS curve captured during the fibril formation process. This curve was used to obtain and characterise the structural kinetics of cluster 1 studying the process of fibrils formation with TR-SAXS.The quoted 'expected MW' is that calculated from the amino acid sequence of the monomeric form of the protein.

Amyloid-beta precursor protein (Aß1-42)
Mol. type   Protein
Organism   Homo sapiens
Olig. state   Unknown
Mon. MW   4.5 kDa
 
UniProt   P05067 (672-713)
Sequence   FASTA