Autism associated SHANK3 missense point mutations impact conformational fluctuations and protein turnover at synapses.

Bucher M, Niebling S, Han Y, Molodenskiy D, Nia FH, Kreienkamp HJ, Svergun D, Kim E, Kostyukova AS, Kreutz MR, Mikhaylova M, Elife 10 (2021) Europe PMC

SASDLK3 – SH3 and multiple ankyrin repeat domains protein 3 with a point mutation (L68P)

SH3 and multiple ankyrin repeat domains protein 3
MWexperimental 83 kDa
MWexpected 88 kDa
VPorod 224 nm3
log I(s) 4.22×10-2 4.22×10-3 4.22×10-4 4.22×10-5
SH3 and multiple ankyrin repeat domains protein 3 small angle scattering data  s, nm-1
ln I(s)
SH3 and multiple ankyrin repeat domains protein 3 Guinier plot ln 4.22×10-2 Rg: 4.1 nm 0 (4.1 nm)-2 s2
(sRg)2I(s)/I(0)
SH3 and multiple ankyrin repeat domains protein 3 Kratky plot 1.104 0 √3 sRg
p(r)
SH3 and multiple ankyrin repeat domains protein 3 pair distance distribution function Rg: 4.6 nm 0 Dmax: 14.8 nm

Data validation

Fits and models

log I(s)
 s, nm-1
SH3 and multiple ankyrin repeat domains protein 3 CORAL model
log I(s)
 s, nm-1
SH3 and multiple ankyrin repeat domains protein 3 CORAL model
Synchrotron SAXS data from solutions of SH3 and multiple ankyrin repeat domains protein 3 with a point mutation (L68P) in 100mM NaH2PO4, 100mM NaCl, 0.5mM DTT,, pH 6.5 were collected on the EMBL P12 beam line at the PETRA III storage ring (DESY; Hamburg, Germany) using a Pilatus 2M 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). Solute concentrations ranging between 0.5 and 4 mg/ml were measured at 10°C. 20 successive 0.500 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. The low angle data collected at lower concentrations were extrapolated to infinite dilution and merged with the higher concentration data to yield the final composite scattering curve.

SH3 and multiple ankyrin repeat domains protein 3 (SHANK3)
Mol. type   Protein
Organism   Rattus norvegicus
Olig. state   Monomer
Mon. MW   87.5 kDa
 
UniProt   Q9JLU4 (1-676)
Sequence   FASTA