1.A.1.10.19
Sodium channel Nav1.4-beta complex of 1820 and 209 aas, respectively. Voltage-gated sodium (Nav) channels initiate and propagate action potentials. Yan et al. 2017 presented the cryo-EM structure of EeNav1.4, the Nav channel from electric eel, in complex with the beta1 subunit at 4.0 Å resolution. The immunoglobulin domain of beta1 docks onto the extracellular L5I and L6IV loops of EeNav1.4 via extensive polar interactions, and the single transmembrane helix interacts with the third voltage-sensing domain (VSDIII). The VSDs exhibit ""up"" conformations, while the intracellular gate of the pore domain is kept open by a digitonin-like molecule. Structural comparison with closed NavPaS shows that the outward transfer of gating charges is coupled to the iris-like pore domain dilation through intricate force transmissions involving multiple channel segments. The IFM fast inactivation motif on the III-IV linker is plugged into the corner enclosed by the outer S4-S5 and inner S6 segments in repeats III and IV, suggesting a potential allosteric blocking mechanism for fast inactivation (Yan et al. 2017). The PDB# for the complex is 5XSY, and that for the two subunits are 5XSY_A and 5XSY_B. Domain 4 TMS 6 of Nav1.4 plays a key role in channel gating regulation, and is targeted by the neurotoxin, veratridine (VTD) (Niitsu et al. 2018).
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| Accession Number: | P02719 |
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| Protein Name: | Sodium channel protein |
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| Length: | 1820 |
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| Molecular Weight: | 208332.00 |
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| Species: | Electrophorus electricus (Electric eel) [8005] |
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| Number of TMSs: | 23 |
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| Location1 / Topology2 / Orientation3: |
Cell membrane1 / Multi-pass membrane protein2 |
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| Substrate |
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1: MARKFSSARP EMFRRFTPDS LEEIEAFTEL KKSCTLEKKE PESTPRIDLE AGKPLPMIYG
61: DPPEDLLNIP LEDLDPFYKT QKTFIVISKG NIINRFNAER ALYIFSPFNP IRRGAIRVFV
121: NSAFNFFIMF TIFSNCIFMT ISNPPAWSKI VEYTFTGIYT FEVIVKVLSR GFCIGHFTFL
181: RDPWNWLDFS VVTMTYITEF IDLRNVSALR TFRVLRALKT ITIFPGLKTI VRALIESMKQ
241: MGDVVILTVF SLAVFTLAGM QLFMGNLRHK CIRWPISNVT LDYESAYNTT FDFTAYIENE
301: ENQYFLDGAL DALLCGNNSD AGKCPEGYTC MKAGRNPNYG YTNYDNFAWT FLCLFRLMLQ
361: DYWENLYQMT LRAAGKSYMV FFIMVIFLGS FYLINLILAV VAMAYEEQNQ ATLAEAQEKE
421: AEFQRAVEQL RIQQEQINDE RKASLASQLT QNQEAEITDD GDDAIKECNG KAFPLANIRE
481: PSSVKLSTEE QRSDSKSMDS KHSVDKPSLK HKAASTMSVF TLEDLEAARR PCPPVWYKFA
541: GFVFKWNCCG PWVFLKKWVH FVMMDPFTDL FITLCIILNT LFMSIEHHPM NESFQSLLSA
601: GNLVFTTIFA AEMVLKIIAL DPYYYFQQTW NIFDSIIVSL SLLELGLSNM QGMSVLRSLR
661: LLRIFKLAKS WPTLNILIKI ICNSVGALGN LTIVLAIIVF IFALVGFQLF GKNYKEYVCK
721: ISDDCELPRW HMNDFFHSFL IVFRALCGEW IETMWDCMEV GGVPMCLAVY MMVIIIGNLV
781: MLNLFLALLL SSFSSDNLSS IEEDDEVNSL QVASERISRA KNWVKIFITG TVQALVLWIQ
841: GKKPPSDDVV GEEGDNEGKK DTLPLNYLDG EKIVDGITNC VESPTLNLPI VKGESEIEEE
901: GLVDSSDEED TNKKKHALND EDSSVCSTVD YSPSEQDPLA KEEEEEEEEE PEELESKDPE
961: ACFTEKCIWR FPFLDVDITQ GKGKIWWNLR RTCYTIVEHD YFETFIIFMI LLSSGVLAFE
1021: DIYIWRRRVI KVILEYADKV FTYVFIVEML LKWVAYGFKR YFTDAWCWLD FVIVGASIMG
1081: ITSSLLGYEE LGAIKNLRTI RALRPLRALS RFEGMKVVVR ALLGAIPSIM NVLLVCLMFW
1141: LIFSIMGVNL FAGKFYRCIN TTTDEILPVE EVNNRSDCMA LMYTNEVRWV NLKVNYDNAG
1201: MGYLSLLQVS TFKGWMDIMY AAVDSREVED QPIYEINVYM YLYFVIFIVF GAFFTLNLFI
1261: GVIIDNFNRQ KQKLGGEDLF MTEEQKKYYN AMKKLGSKKA AKCIPRPSNV VQGVVYDIVT
1321: QPFTDIFIMA LICINMVAMM VESEDQSQVK KDILSQINVI FVIIFTVECL LKLLALRQYF
1381: FTVGWNVFDF AVVVISIIGL LLSDIIEKYF VSPTLFRVIR LARIARVLRL IRAAKGIRTL
1441: LFALMMSLPA LFNIGLLLFL IMFIFSIFGM SNFAYVKKQG GVDDIFNFET FGNSMICLFE
1501: ITTSAGWDGL LLPTLNTGPP DCDPDVENPG TDVRGNCGNP GKGITFFCSY IILSFLVVVN
1561: MYIAIILENF GVAQEESSDL LCEDDFVMFD ETWHKFDVHG TQFLDYNDLP RFVNALQEPM
1621: RIPNPNRHKL AKMDMYVVME DKISYLDVLL AVTQEVLGDT TEMEAMRLSI QAKFKKDNPS
1681: PTFFEPVVTT LRRKEEEWAS VVIQRAFRQY LLMRAVSHAS FLSQIKHMNE GPKDGVGSQD
1741: SLITQKMNAL YRGNPELTMP LEQQIKPMLD KPRMPSLSVP ETYPIQIPKE VTNEVILHSA
1801: PMVRQNYSYS GAIVVRESIV