Ligands binding to the prion protein induce its proteolytic release with therapeutic potential in neurodegenerative proteinopathies.

Linsenmeier L, Mohammadi B, Shafiq M, Frontzek K, Bär J, Shrivastava AN, Damme M, Song F, Schwarz A, Da Vela S, Massignan T, Jung S, Correia A, Schmitz M, Puig B, Hornemann S, Zerr I, Tatzelt J, Biasini E, Saftig P, Schweizer M, Svergun D, Amin L, Mazzola F, Varani L, Thapa S, Gilch S, Schätzl H, Harris DA, Triller A, Mikhaylova M, Aguzzi A, Altmeppen HC, Glatzel M, Sci Adv 7(48):eabj1826 (2021) Europe PMC

SASDLT2 – 6D11 IgG monoclonal antibody

Anti-prion protein monoclonal IgG2a 6D11
MWI(0) 120 kDa
MWexpected 145 kDa
VPorod 330 nm3
log I(s) 9.29×10-2 9.29×10-3 9.29×10-4 9.29×10-5
Anti-prion protein monoclonal IgG2a 6D11 small angle scattering data  s, nm-1
ln I(s)
Anti-prion protein monoclonal IgG2a 6D11 Guinier plot ln 9.29×10-2 Rg: 5.1 nm 0 (5.1 nm)-2 s2
Anti-prion protein monoclonal IgG2a 6D11 Kratky plot 1.104 0 3 sRg
Anti-prion protein monoclonal IgG2a 6D11 pair distance distribution function Rg: 5.2 nm 0 Dmax: 17.4 nm

Data validation

Fits and models

log I(s)
 s, nm-1
Anti-prion protein monoclonal IgG2a 6D11 CORAL model

Synchrotron SAXS data from solutions of 6D11 IgG monoclonal antibody in PBS, pH 7.4 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 = 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. 60 successive 0.095 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 data were acquired as a concentration series in the range 0.75 - 2.0 mg/mL. All the SAXS curves overlap well, and the curve at 2 mg/mL was employed for parameter estimation and modeling.

Anti-prion protein monoclonal IgG2a 6D11 (6D11)
Mol. type   Protein
Organism   Mus musculus
Olig. state   Monomer
Mon. MW   145.2 kDa
Sequence   FASTA