Structural basis for antibody-mediated NMDA receptor clustering and endocytosis in autoimmune encephalitis.

Wang H, Xie C, Deng B, Ding J, Li N, Kou Z, Jin M, He J, Wang Q, Wen H, Zhang J, Zhou Q, Chen S, Chen X, Yuan TF, Zhu S, Nat Struct Mol Biol (2024) Europe PMC

SASDR72 – Human GluN1-GluN2A NMDA receptor in complex with human derived autoantibody mAb5F6 at pH 8.0

Glutamate receptor ionotropic, NMDA 1
Glutamate receptor ionotropic, NMDA 2A
Human derived autoantibody mAb5F6 heavy chain, mAb5F6 VH
Human derived autoantibody mAb5F6 light chain, mAb5F6 VL
MWexperimental 975 kDa
MWexpected 539 kDa
VPorod 2500 nm3
log I(s) 3.08×102 3.08×101 3.08×100 3.08×10-1
Glutamate receptor ionotropic, NMDA 1 Glutamate receptor ionotropic, NMDA 2A Human derived autoantibody mAb5F6 heavy chain, mAb5F6 VH Human derived autoantibody mAb5F6 light chain, mAb5F6 VL small angle scattering data  s, nm-1
ln I(s)
Glutamate receptor ionotropic, NMDA 1 Glutamate receptor ionotropic, NMDA 2A Human derived autoantibody mAb5F6 heavy chain, mAb5F6 VH Human derived autoantibody mAb5F6 light chain, mAb5F6 VL Guinier plot ln 3.08×102 Rg: 9.9 nm 0 (9.9 nm)-2 s2
(sRg)2I(s)/I(0)
Glutamate receptor ionotropic, NMDA 1 Glutamate receptor ionotropic, NMDA 2A Human derived autoantibody mAb5F6 heavy chain, mAb5F6 VH Human derived autoantibody mAb5F6 light chain, mAb5F6 VL Kratky plot 1.104 0 3 sRg
p(r)
Glutamate receptor ionotropic, NMDA 1 Glutamate receptor ionotropic, NMDA 2A Human derived autoantibody mAb5F6 heavy chain, mAb5F6 VH Human derived autoantibody mAb5F6 light chain, mAb5F6 VL pair distance distribution function Rg: 10.5 nm 0 Dmax: 31.7 nm

Data validation


There are no models related to this curve.

Synchrotron SAXS data from solutions of human GluN1-GluN2A NMDA receptor in complex with human derived autoantibody mAb5F6 in 150 mM NaCl, 0.1% digitonin, 5 µM cholesteryl hemisuccinate (TRIS salt), 0.1 mM CHAPSO, 50 µM EDTA,1 mM Gly/Glu, 20 mM HEPES, pH 8 were collected on the BL19U2 beam line at the Shanghai Synchrotron Radiation Facility (SSRF; Shanghai, China) using a Pilatus 1M detector at a sample-detector distance of 2.7 m and at a wavelength of λ = 0.1033 nm (I(s) vs s, where s = 4πsinθ/λ, and 2θ is the scattering angle). One solute concentration of 0.60 mg/ml was measured at 10°C. 20 successive 1 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.

Dmax appears underestimated.

Glutamate receptor ionotropic, NMDA 1
Mol. type   Protein
Organism   Homo sapiens
Olig. state   Dimer
Mon. MW   96.5 kDa
 
UniProt   Q05586 (1-847)
Sequence   FASTA
 
Glutamate receptor ionotropic, NMDA 2A
Mol. type   Protein
Organism   Homo sapiens
Olig. state   Dimer
Mon. MW   95.5 kDa
 
UniProt   Q12879 (1-842)
Sequence   FASTA
 
Human derived autoantibody mAb5F6 heavy chain, mAb5F6 VH
Mol. type   Protein
Organism   Homo sapiens
Olig. state   Dimer
Mon. MW   51.8 kDa
Sequence   FASTA
 
Human derived autoantibody mAb5F6 light chain, mAb5F6 VL
Mol. type   Protein
Olig. state   Dimer
Mon. MW   25.9 kDa
Sequence   FASTA