Fig 1.
Schematic representation of the Filamin-A (FLNa) homodimer.
The structural and functional domains, and the reported liveborn PNH male variants in the literature were represented on associated region of the structure. The variants subjected to molecular dynamics simulations are shown in bold. †aa: amino acid.
Fig 2.
Pedigree and electropherograms of a non-consanguineous Turkish family segregating X-linked dominant periventricular nodular heterotopia.
Two hemizygous brothers carry the novel c.1451G>A (p.Arg484Gln) variant. Asymptomatic mother is a heterozygous carrier of the variant. Father carries the reference allele.
Table 1.
The filamin-A (FLNa) variants reported in the liveborn male patients with periventricular nodular heterotopia.
The full list given in S1 Table was filtered into this list to be able to study the impact of the variants via molecular dynamics simulations.
Table 2.
Approximate dimensions and atom count of the systems prepared for molecular dynamics simulations, and simulation time lengths.
Fig 3.
Average Cα root-mean-square fluctuations (RMSF) of the amino acids during the simulations.
Only the regions whose flexibility is affected by the variants are demonstrated. They are highlighted on the cartoon representation of the structural parts of filamin-A (FLNa): (A) FLNaABD, (B) IgFLNa3-5, (C) IgFLNa21 and (D) IgFLNa24. †Colored stars at the bottom of the panels and the colored regions on the structure representation refer to the same region on FLNa.
Fig 4.
Conformational spaces of the (A) FLNaABD, (B) IgFLNa3-5, (C) IgFLNa21 and (D) IgFLNa24 variants, compared to the wild-type.
The conformations collected in the molecular dynamics simulations are visualized by using the first two principal components.
Fig 5.
Backbone root-mean-square deviations (RMSD) and visualizations of known critical regions for cell migration.
The following structural parts of filamin-A (FLNa) were represented: (A) FLNaABD, (B) IgFLNa3-5, (C) IgFLNa21 and (D) IgFLNa24. The critical regions were helix-A, a putative ligand-binding site, a ligand-binding site and dimerization interface for these parts, respectively.