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Fig. 2 | BMC Medical Genomics

Fig. 2

From: WFS1 autosomal dominant variants linked with hearing loss: update on structural analysis and cochlear implant outcome

Fig. 2

3D modeling and structural analysis of WFS1 p.Ala684Val. (A) WFS1 3D model generated from Alphafold (green). Ala684/Arg685 are located at the alpha-helix (Cyan, Met683-His692) of the ER-luminal domain. (B) Putative WFS1(Alphafold model) – NCS1(4GUK) interaction model generated by PyDock software. Arg685 extrudes from alpha helix (helix A) and directly interacts with NCS1 Phe50 via cation-π interaction (black dashes). (C) Loss of WFS1-NCS1 interaction in p.Arg685Pro. The p.Arg685Pro mutant loses its own cation- π interaction, which is required for WFS1-NCS1 interaction. Moreover, proline substitution breaks helix A [1], contributing to the loss of NCS1 interaction [2]. (D) Non-polar, hydrophobic substitution of A684 induces helix destabilization and distorts helix A [1]. The side chain of R685 in twisted helix A may tilt from its original position [2], disrupting NCS1 binding [3] (grey dashes)

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BMC Medical Genomics

ISSN: 1755-8794

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