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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-30400 | |||||||||
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Title | Cryo-EM structure of human NALCN in complex with FAM155A | |||||||||
![]() | Main map | |||||||||
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Function / homology | ![]() positive regulation of synaptic transmission, cholinergic / leak channel activity / regulation of resting membrane potential / sodium channel activity / voltage-gated sodium channel activity / monoatomic ion channel complex / calcium ion import across plasma membrane / sodium ion transmembrane transport / monoatomic cation channel activity / potassium ion transmembrane transport ...positive regulation of synaptic transmission, cholinergic / leak channel activity / regulation of resting membrane potential / sodium channel activity / voltage-gated sodium channel activity / monoatomic ion channel complex / calcium ion import across plasma membrane / sodium ion transmembrane transport / monoatomic cation channel activity / potassium ion transmembrane transport / monoatomic ion transmembrane transport / positive regulation of synaptic transmission, GABAergic / calcium ion transmembrane transport / Stimuli-sensing channels / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
![]() | Wu J / Yan Z / Ke M | |||||||||
![]() | ![]() Title: Structure of the human sodium leak channel NALCN in complex with FAM155A. Authors: Jiongfang Xie / Meng Ke / Lizhen Xu / Shiyi Lin / Jin Huang / Jiabei Zhang / Fan Yang / Jianping Wu / Zhen Yan / ![]() Abstract: NALCN, a sodium leak channel expressed mainly in the central nervous system, is responsible for the resting Na permeability that controls neuronal excitability. Dysfunctions of the NALCN ...NALCN, a sodium leak channel expressed mainly in the central nervous system, is responsible for the resting Na permeability that controls neuronal excitability. Dysfunctions of the NALCN channelosome, NALCN with several auxiliary subunits, are associated with a variety of human diseases. Here, we report the cryo-EM structure of human NALCN in complex with FAM155A at an overall resolution of 3.1 angstroms. FAM155A forms extensive interactions with the extracellular loops of NALCN that may help stabilize NALCN in the membrane. A Na ion-binding site, reminiscent of a Ca binding site in Ca channels, is identified in the unique EEKE selectivity filter. Despite its 'leaky' nature, the channel is closed and the intracellular gate is sealed by S6, II-III linker and III-IV linker. Our study establishes the molecular basis of Na permeation and voltage sensitivity, and provides important clues to the mechanistic understanding of NALCN regulation and NALCN channelosome-related diseases. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 4.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21 KB 21 KB | Display Display | ![]() |
Images | ![]() | 38.2 KB | ||
Others | ![]() ![]() ![]() ![]() | 833.9 KB 553.3 KB 49 MB 49 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7cm3MC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Main map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.087 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Extracellular region
File | emd_30400_additional_1.map | ||||||||||||
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Annotation | Extracellular region | ||||||||||||
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-Additional map: Intracellular region
File | emd_30400_additional_2.map | ||||||||||||
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Annotation | Intracellular region | ||||||||||||
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-Half map: half map1
File | emd_30400_half_map_1.map | ||||||||||||
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Annotation | half map1 | ||||||||||||
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-Half map: halp map2
File | emd_30400_half_map_2.map | ||||||||||||
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Annotation | halp map2 | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Binary complex of human NALCN with FAM155A
Entire | Name: Binary complex of human NALCN with FAM155A |
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Components |
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-Supramolecule #1: Binary complex of human NALCN with FAM155A
Supramolecule | Name: Binary complex of human NALCN with FAM155A / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Sodium leak channel non-selective protein
Macromolecule | Name: Sodium leak channel non-selective protein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 203.616953 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MLKRKQSSRV EAQPVTDFGP DESLSDNADI LWINKPWVHS LLRICAIISV ISVCMNTPMT FEHYPPLQYV TFTLDTLLMF LYTAEMIAK MHIRGIVKGD SSYVKDRWCV FDGFMVFCLW VSLVLQVFEI ADIVDQMSPW GMLRIPRPLI MIRAFRIYFR F ELPRTRIT ...String: MLKRKQSSRV EAQPVTDFGP DESLSDNADI LWINKPWVHS LLRICAIISV ISVCMNTPMT FEHYPPLQYV TFTLDTLLMF LYTAEMIAK MHIRGIVKGD SSYVKDRWCV FDGFMVFCLW VSLVLQVFEI ADIVDQMSPW GMLRIPRPLI MIRAFRIYFR F ELPRTRIT NILKRSGEQI WSVSIFLLFF LLLYGILGVQ MFGTFTYHCV VNDTKPGNVT WNSLAIPDTH CSPELEEGYQ CP PGFKCMD LEDLGLSRQE LGYSGFNEIG TSIFTVYEAA SQEGWVFLMY RAIDSFPRWR SYFYFITLIF FLAWLVKNVF IAV IIETFA EIRVQFQQMW GSRSSTTSTA TTQMFHEDAA GGWQLVAVDV NKPQGRAPAC LQKMMRSSVF HMFILSMVTV DVIV AASNY YKGENFRRQY DEFYLAEVAF TVLFDLEALL KIWCLGFTGY ISSSLHKFEL LLVIGTTLHV YPDLYHSQFT YFQVL RVVR LIKISPALED FVYKIFGPGK KLGSLVVFTA SLLIVMSAIS LQMFCFVEEL DRFTTFPRAF MSMFQILTQE GWVDVM DQT LNAVGHMWAP VVAIYFILYH LFATLILLSL FVAVILDNLE LDEDLKKLKQ LKQSEANADT KEKLPLRLRI FEKFPNR PQ MVKISKLPSD FTVPKIRESF MKQFIDRQQQ DTCCLLRSLP TTSSSSCDHS KRSAIEDNKY IDQKLRKSVF SIRARNLL E KETAVTKILR ACTRQRMLSG SFEGQPAKER SILSVQHHIR QERRSLRHGS NSQRISRGKS LETLTQDHSN TVRYRNAQR EDSEIKMIQE KKEQAEMKRK VQEEELRENH PYFDKPLFIV GREHRFRNFC RVVVRARFNA SKTDPVTGAV KNTKYHQLYD LLGLVTYLD WVMIIVTICS CISMMFESPF RRVMHAPTLQ IAEYVFVIFM SIELNLKIMA DGLFFTPTAV IRDFGGVMDI F IYLVSLIF LCWMPQNVPA ESGAQLLMVL RCLRPLRIFK LVPQMRKVVR ELFSGFKEIF LVSILLLTLM LVFASFGVQL FA GKLAKCN DPNIIRREDC NGIFRINVSV SKNLNLKLRP GEKKPGFWVP RVWANPRNFN FDNVGNAMLA LFEVLSLKGW VEV RDVIIH RVGPIHGIYI HVFVFLGCMI GLTLFVGVVI ANFNENKGTA LLTVDQRRWE DLKSRLKIAQ PLHLPPRPDN DGFR AKMYD ITQHPFFKRT IALLVLAQSV LLSVKWDVED PVTVPLATMS VVFTFIFVLE VTMKIIAMSP AGFWQSRRNR YDLLV TSLG VVWVVLHFAL LNAYTYMMGA CVIVFRFFSI CGKHVTLKML LLTVVVSMYK SFFIIVGMFL LLLCYAFAGV VLFGTV KYG ENINRHANFS SAGKAITVLF RIVTGEDWNK IMHDCMVQPP FCTPDEFTYW ATDCGNYAGA LMYFCSFYVI IAYIMLN LL VAIIVENFSL FYSTEEDQLL SYNDLRHFQI IWNMVDDKRE GVIPTFRVKF LLRLLRGRLE VDLDKDKLLF KHMCYEME R LHNGGDVTFH DVLSMLSYRS VDIRKSLQLE ELLAREQLEY TIEEEVAKQT IRMWLKKCLK RIRAKQQQSC SIIHSLRES QQQELSRFLN PPSIETTQPS EDTNANSQDN SMQPETSSQQ QLLSPTLSDR GGSRQDAADA GKPQRKFGQW RLPSAPKPIS HSVSSVNLR FGGRTTMKSV VCKMNPMTDA ASCGSEVKKW WTRQLTVESD ESGDDLLDIL EDEVDAGSDY KDDDDKGSDY K DDDDK |
-Macromolecule #2: Transmembrane protein FAM155A
Macromolecule | Name: Transmembrane protein FAM155A / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 54.604438 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MTRGAWMCRQ YDDGLKIWLA APRENEKPFI DSERAQKWRL SLASLLFFTV LLSDHLWFCA EAKLTRARDK EHQQQQRQQQ QQQQQQRQR QQQQQQRRQQ EPSWPALLAS MGESSPAAQA HRLLSASSSP TLPPSPGDGG GGGGKGNRGK DDRGKALFLG N SAKPVWRL ...String: MTRGAWMCRQ YDDGLKIWLA APRENEKPFI DSERAQKWRL SLASLLFFTV LLSDHLWFCA EAKLTRARDK EHQQQQRQQQ QQQQQQRQR QQQQQQRRQQ EPSWPALLAS MGESSPAAQA HRLLSASSSP TLPPSPGDGG GGGGKGNRGK DDRGKALFLG N SAKPVWRL ETCYPQGASS GQCFTVENAD AVCARNWSRG AAGGDGQEVR SKHPTPLWNL SDFYLSFCNS YTLWELFSGL SS PNTLNCS LDVVLKEGGE MTTCRQCVEA YQDYDHHAQE KYEEFESVLH KYLQSEEYSV KSCPEDCKIV YKAWLCSQYF EVT QFNCRK TIPCKQYCLE VQTRCPFILP DNDEVIYGGL SSFICTGLYE TFLTNDEPEC CDVRREEKSN NPSKGTVEKS GSCH RTSLT VSSATRLCNS RLKLCVLVLI LLHTVLTASA AQNTAGLSFG GINTLEENST NEELEDEVDA GSDYKDDDDK GSDYK DDDD K |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 2 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Macromolecule #6: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE
Macromolecule | Name: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE / type: ligand / ID: 6 / Number of copies: 10 / Formula: PC1 |
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Molecular weight | Theoretical: 790.145 Da |
Chemical component information | ![]() ChemComp-PC1: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: NONE / Details: Ab Initio |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 65177 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |