The structure of pathogenic huntingtin exon 1 defines the bases of its aggregation propensity.

Elena-Real CA, Sagar A, Urbanek A, Popovic M, Morató A, Estaña A, Fournet A, Doucet C, Lund XL, Shi ZD, Costa L, Thureau A, Allemand F, Swenson RE, Milhiet PE, Crehuet R, Barducci A, Cortés J, Sinnaeve D, Sibille N, Bernadó P, Nat Struct Mol Biol (2023) Europe PMC

SASDQS8 – Exon1 of Pathogenic form of Huntingtin (H46) with GFP fused at the C-terminus

MWexperimental 56 kDa
MWexpected 43 kDa
log I(s) 2.11×10-2 2.11×10-3 2.11×10-4 2.11×10-5
Huntingtin small angle scattering data  s, nm-1
ln I(s)
Huntingtin Guinier plot ln 2.11×10-2 Rg: 4.2 nm 0 (4.2 nm)-2 s2
Huntingtin Kratky plot 1.104 0 3 sRg

Data validation

Fits and models

log I(s)
 s, nm-1
Huntingtin OTHER [STATIC IMAGE] model

Synchrotron SAXS data from solutions of exon1 of the pathogenic form of Huntingtin (H46) with GFP fused at the C-terminus in 20mM BisTris-HCl, 150mM NaCl, pH 6.5 were collected on the EMBL P12 beam line at PETRA III (DESY, Hamburg, Germany) using a Pilatus 6M detector at a sample-detector distance of 3 m and at a wavelength of λ = 1.2398 nm (I(s) vs s, where s = 4πsinθ/λ, and 2θ is the scattering angle). In-line size-exclusion chromatography (SEC) SAS was employed. The SEC parameters were as follows: A 50.00 μl sample at 8 mg/ml was injected at a 0.50 ml/min flow rate onto a GE Superdex 200 Increase 10/300 column at 10°C. 1680 successive 0.245 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.

Huntingtin (H46)
Mol. type   Protein
Organism   Homo sapiens
Olig. state   Monomer
Mon. MW   43.0 kDa
UniProt   P42858 (1-88)
Sequence   FASTA
PED ID   PED00224