Fig. 5
From: Network topology of NaV1.7 mutations in sodium channel-related painful disorders
Network inter-residue connectivity of the IEM-associated mutations I848T and N395K. a The graph shows the NaV1.7 sodium channel topology and highlights the amino acids I848 (DI; S4-S5) and N395 (DI; S6). Inter-domain bond interaction are depicted in red for the IEM associated mutation I848T and in green for the IEM associated mutation N395K. b Upper panels show I848 and T848 networks, lower panels show N395 and K395 network. Bct and EBct evidence interatomic traffic over the network. Red-to-white color gradient of amino acids (nodes) represents Bct value (red represents high Bct and white low Bct). Red-to-black color gradient of edges (amino acid interatomic interactions) corresponds to EBct value (red represents high EBct and black low EBct). Hydrophobic bonds are showed in solid lines and H-bonds are indicated by dashed lines. I848 present high EB ct of connecting different parts of the NaV1.7 network. Upper right panels show that I848 interacts through hydrophobic interactions with S4-S5 (DII) and pore (DIII) through I845 and F1435 that are two residues having very high B ct values (3.4 and 6.6, respectively) and H-bonds with V852 and L844 (I848[CO] with V852[NH]; I848[NH] with L844[CO]). Note the difference of Bct of the upper left panel (I848Bct = 7.36) compared to the upper right panel (T848Bct = 1.52). I848T mutation interrupts the shortest paths within the network between DII (S4-S5) and DIII (pore) and therefore ΔB ct shifts to a negative value (-5.84). T848 interacts with F1435 through hydrophobic interactions and with S851 and L844 through H-bonds (T848[CO] with S851[NH]; T848[NH] with L844[CO]; T848[HG1] with L844[CO]). Lower panels show that N395 amino acid (red, S6 in pore module in DI) interacts with L1626 (S4-S5) via hydrophobic bond and via H-bonds formed by N395[CO] and A399[NH]and N395[NH]and F391[CO]. K395 mutation creates new hydrophobic bonds with V248 (S4-S5, DI), K398 (S6, DI), V1747 (S6, DIV), L1622 (S4-S5, DIV) and new H-bonds formed by K395[NZ] with N1751[CG] (S6, DIV) and K395[NZ] with A1625[CO] (S4-S5, DIV). These new bonds create a novel communication path within the network and thus increase Bct value of the residue 395 (K395Bct = 7.76 compared to the left panel N395Bct = 2.44). Edge thickness are proportional to EB ct and reveal that a high number of shortest paths pass through few edges