Comprehensive biophysical and structural profiling of alpha-actinin-2 variants reveals mechanistic diversity in hypertrophic cardiomyopathy.

Noureddine M Mikolajek H, Cowieson N, Pinotsis N, Robinson P, Slater A, Redwood C, Loughna S, Denning C, Mohammed F, Gehmlich K, Nat Commun 17(1) (2026) Europe PMC

SASDZN5 – ACTN2-R93Q using SEC-SAXS (dimer peak)

Alpha-actinin-2
MWexperimental 245 kDa
MWexpected 208 kDa
log I(s) 9.90×10-2 9.90×10-3 9.90×10-4 9.90×10-5
Alpha-actinin-2 small angle scattering data  s, nm-1
ln I(s)
Alpha-actinin-2 Guinier plot ln 9.90×10-2 Rg: 11.6 nm 0 (11.6 nm)-2 s2
(sRg)2I(s)/I(0)
Alpha-actinin-2 Kratky plot 1.104 0 √3 sRg
p(r)
Alpha-actinin-2 pair distance distribution function Rg: 11.3 nm 0 Dmax: 37 nm

Data validation

There are no models related to this curve.

Synchrotron SAXS data from solutions of ACTN2-R93Q using SEC-SAXS (dimer peak) in 20 mM HEPES, 150 mM NaCl, pH 8 were collected on the B21 beam line at the Diamond Light Source storage ring (Didcot, UK) using a Eiger 4M detector at a sample-detector distance of 3.7 m and at a wavelength of λ = 0.94 nm (I(s) vs s, where s = 4πsinθ/λ, and 2θ is the scattering angle). One solute concentration of 5.00 mg/ml was measured at 4°C. 600 successive 3.200 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.

ACTN2 with R93Q variant, using SEC-SAXS (dimer peak selected)

Alpha-actinin-2 (ACTN2)
Mol. type   Protein
Organism   Homo sapiens
Olig. state   Dimer
Mon. MW   103.9 kDa
 
UniProt   P35609
Sequence   FASTA