FIGURE 1.

The conserved R596 residue is predicted to have a critical role in stabilizing the interaction between α₂ and δ peptides. (a) Sequence alignment between α₂δ‐2 proteins from different species. Position corresponding to human arginine 593 (R596 in mouse α₂δ‐2) is highlighted in purple. (b) Schematic overview of α₂δ‐2 protein illustrating the positions of the von Willebrand factor type A domain (VWA) and the p.R596P mutation. (c) Structural homology modeling of mouse α₂δ‐2 protein based on the published Cryo‐EM structure of the human Ca_V2.2 channel complex (PDB code: 7MIY) predicts a critical interaction of the side chain of R596 (α₂ peptide) with the backbone of Y1094 residue (δ peptide) through a hydrogen bond. (Color code: α₂ peptide in purple, VWA domain in orange, and δ peptide in pink.) AlphaFold per‐residue model confidence scores (pLDDT) for R596 and Y1094 residues are very high (97.38 and 94.25, respectively).