Fig. 4
From: Network topology of NaV1.7 mutations in sodium channel-related painful disorders
Structural modelling of NaV1.7 variants and their interatomic bonds. a The graph shows the NaV1.7 sodium channel topology and highlights the IEM associated mutation F216S and its intra-domain bond interaction (S3 and S4; depicted in red). b Upper left inset shows the intramembrane view of the NaV1.7 channel and the amino acid F216. Upper right inset shows network view of the four NaV1.7 channel domains (DI, purple; DII, green; DIII, light blue; DIV, orange); the topology of amino acid F216 is showed as grey node. Lower insets show the bonds of WT amino acid F216 (left) and mutated amino acid S216 (right). Hydrophobic bonds are showed in green solid lines. H-bonds are showed with yellow dashed lines. F216 (DI, red) interacts with V194, V195, F198, T202 (S3, DI) and L219 (S4, DI) via hydrophobic bonds. F216 interact via H-bonds with L213 (formed by F216[NH] and L213[CO]) and L219 (F216[CO] with L219[NH]) located in S4, DI. The mutation F216S (right) interrupts all the hydrophobic interactions with S3 residues and created new H-bonds (S216[NH] with A212[CO]) causing a decrease of B ct and EB ct values. c The graph shows the NaV1.7 sodium channel topology and highlights the IEM associated mutation L858H and its inter-domain bond interaction (S4-S5 and S4; depicted in red). d Upper left inset shows the intramembrane view of the NaV1.7 channel and the amino acid L858. Upper right insets show network view of the four NaV1.7 channeldomains (DI, purple; DII, green; DIII, light blue; DIV, orange); the topology of amino acid L858 is showed as grey node. Lower inset shows the bonds of WT amino acid L858 (left) and mutated amino acid H858 (right). Hydrophobic bonds are showed in green solid lines. H-bonds are indicated by yellow dashed lines. L858 residue (red, S4-S5; DII) interacts with I234 (DI; S4-S5), V861 (DII; S4-S5), N950, L951 and V947 (DII; S6) through hydrophobic bonds and through H-bonds with L862 (formed by L858[CO] and L862[NH]) located in DII; S4-S5. L858H mutation interrupts hydrophobic interaction with I234 (DI; S4-S5), V861 (DII; S4-S5), N950 and forms new H-bonds with A854 (formed by H858[NH] and A854[CO]) (DII; S4-S5) and V947 (formed by H858[NE2] and V947[CO]) (DII; S6). These changes decrease B ct value of amino acid 858 from 2.2 to 0.39. e The graph shows the NaV1.7 sodium channel topology and highlights the nABN mutation L1267V that is located in the domain DIII; S3 depicted in red. f Upper left inset show the intramembrane view of the NaV1.7 channel and the amino acid L1267. Upper right inset shows network view of the four NaV1.7 channel domains (DI, purple; DII, green; DIII, light blue; DIV, orange); the topology of amino acid L1267 is showed as grey node. Lower inset show the bonds of WT amino acid L1267 (left) and mutated amino acid V1267 (right). Hydrophobic bonds are showed in green solid lines. H-bonds are indicated by yellow dashed lines. L1267[NH] (VSD in DIII) interacts through H-bonds with V1263[CO]. V1267mutation interacts with V1263 through a hydrophobic bond. This change does not modify B ct value of the residue 1267