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- EMDB-54419: Cryo-EM structure of human NHE6 in C2 symmetry -

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Basic information

Entry
Database: EMDB / ID: EMD-54419
TitleCryo-EM structure of human NHE6 in C2 symmetry
Map data
Sample
  • Complex: Homodimeric human NHE6 in C2 symmetry
    • Protein or peptide: Sodium/hydrogen exchanger 6
KeywordsNHE / C2 symmetry / homodimer / transporter / TRANSPORT PROTEIN
Function / homology
Function and homology information


Defective SLC9A6 causes X-linked, syndromic mental retardation,, Christianson type (MRXSCH) / Sodium/Proton exchangers / dendrite extension / potassium:proton antiporter activity / sodium:proton antiporter activity / axon extension / sodium ion import across plasma membrane / establishment of cell polarity / neuron projection morphogenesis / potassium ion transmembrane transport ...Defective SLC9A6 causes X-linked, syndromic mental retardation,, Christianson type (MRXSCH) / Sodium/Proton exchangers / dendrite extension / potassium:proton antiporter activity / sodium:proton antiporter activity / axon extension / sodium ion import across plasma membrane / establishment of cell polarity / neuron projection morphogenesis / potassium ion transmembrane transport / regulation of intracellular pH / sodium ion transmembrane transport / recycling endosome / recycling endosome membrane / late endosome membrane / early endosome membrane / endoplasmic reticulum membrane / identical protein binding / plasma membrane
Similarity search - Function
Sodium/hydrogen exchanger 6/7/9 / Na+/H+ exchanger / Cation/H+ exchanger, CPA1 family / Cation/H+ exchanger / Sodium/hydrogen exchanger, transmembrane
Similarity search - Domain/homology
Sodium/hydrogen exchanger 6
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsFeilen LP / Sach L / Tranchant EE / Lalic MR / Havelund JF / Brauer CM / Ginsthofer M / Ostendorf J / Ma L / Morrow EM ...Feilen LP / Sach L / Tranchant EE / Lalic MR / Havelund JF / Brauer CM / Ginsthofer M / Ostendorf J / Ma L / Morrow EM / Faergeman NJ / Pedersen SF / Kragelund BB / Autzen HE
Funding support Denmark, European Union, 5 items
OrganizationGrant numberCountry
Novo Nordisk FoundationNNF20OC0060692 Denmark
The Carlsberg FoundationCF20-0533 Denmark
Independent Research Fund Denmark - Medical Sciences1131-00023B Denmark
European Research Council (ERC)101151923European Union
Danish Council for Independent Research3103-00217B Denmark
CitationJournal: To Be Published
Title: Integrative structural analysis of the human endosomal Na/H exchanger NHE6 reveals lipid-modulated gating of the ion-binding site
Authors: Feilen LP / Sach L / Tranchant EE / Lalic MR / Havelund JF / Brauer CM / Ginsthofer M / Ostendorf J / Ma L / Morrow EM / Faergeman NJ / Pedersen SF / Kragelund BB / Autzen HE
History
DepositionJul 16, 2025-
Header (metadata) releaseJul 29, 2026-
Map releaseJul 29, 2026-
UpdateJul 29, 2026-
Current statusJul 29, 2026Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_54419.png

Downloads & links

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Map

FileDownload / File: emd_54419.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
0.73 Å/pix.
x 384 pix.
= 278.4 Å		0.73 Å/pix.
x 384 pix.
= 278.4 Å		0.73 Å/pix.
x 384 pix.
= 278.4 Å

Surface

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Slices (1/2)

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.725 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.012
Minimum - Maximum-0.057899836 - 0.0786353
Average (Standard dev.)0.0000888102 (±0.0015347213)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 278.40002 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_54419_msk_1.map
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Additional map: #1

Fileemd_54419_additional_1.map
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Half map: #1

Fileemd_54419_half_map_1.map
Projections & Slices
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Half map: #2

Fileemd_54419_half_map_2.map
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Sample components

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Entire : Homodimeric human NHE6 in C2 symmetry

EntireName: Homodimeric human NHE6 in C2 symmetry
Components
  • Complex: Homodimeric human NHE6 in C2 symmetry
    • Protein or peptide: Sodium/hydrogen exchanger 6

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Supramolecule #1: Homodimeric human NHE6 in C2 symmetry

SupramoleculeName: Homodimeric human NHE6 in C2 symmetry / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Sodium/hydrogen exchanger 6

MacromoleculeName: Sodium/hydrogen exchanger 6 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 77.988508 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MARRGWRRAP LRRGVGSSPR ARRLMRPLWL LLAVGVFDWA GASDGGGGEA RAMDEEIVSE KQAEESHRQD SANLLIFILL LTLTILTIW LFKHRRARFL HETGLAMIYG LLVGLVLRYG IHVPSDVNNV TLSCEVQSSP TTLLVNVSGK FYEYMLKGEI S SHELNNVQ ...String:
MARRGWRRAP LRRGVGSSPR ARRLMRPLWL LLAVGVFDWA GASDGGGGEA RAMDEEIVSE KQAEESHRQD SANLLIFILL LTLTILTIW LFKHRRARFL HETGLAMIYG LLVGLVLRYG IHVPSDVNNV TLSCEVQSSP TTLLVNVSGK FYEYMLKGEI S SHELNNVQ DNEMLRKVTF DPEVFFNILL PPIIFYAGYS LKRRHFFRNL GSILAYAFLG TAISCFVIGS IMYGCVTLMK VT GQLAGDF YFTDCLLFGA IVSATDPVTV LAIFHELQVD VELYALLFGE SVLNDAVAIV LSSSIVAYQP AGDNSHTFDV TAM FKSIGI FLGIFSGSFA MGAATGVVTA LVTKFTKLRE FQLLETGLFF LMSWSTFLLA EAWGFTGVVA VLFCGITQAH YTYN NLSTE SQHRTKQLFE LLNFLAENFI FSYMGLTLFT FQNHVFNPTF VVGAFVAIFL GRAANIYPLS LLLNLGRRSK IGSNF QHMM MFAGLRGAMA FALAIRDTAT YARQMMFSTT LLIVFFTVWV FGGGTTAMLS CLHIRVGVDS DQEHLGVPEN ERRTTK AES AWLFRMWYNF DHNYLKPLLT HSGPPLTTTL PACCGPIARC LTSPQAYENQ EQLKDDDSDL ILNDGDISLT YGDSTVN TE PATSSAPRRF MGNSSEDALD RELAFGDHEL VIRGTRLVLP MDDSEPPLNL LDNTRHGPA

UniProtKB: Sodium/hydrogen exchanger 6

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration2.63 mg/mL
BufferpH: 7.4
Component:
ConcentrationFormulaName
20.0 mMHEPES2-[4-(2-Hydroxyethyl)piperazin-1-yl]ethane-1-sulfonic acid
150.0 mMNaClsodium chloride
0.034 mMGDNglyco-diosgenin
0.008 mMCHScholesteryl hemisuccinate Tris salt
GridModel: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 45 sec.
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS KRIOS
Specialist opticsEnergy filter - Name: TFS Selectris X
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 4933 / Average electron dose: 49.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.8 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 732718
CTF correctionSoftware - Name: RELION (ver. 5.0-beta) / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL
In silico model: The in silico model was generated using Ab initio reconstruction in RELION 5.0-beta
Final reconstructionNumber classes used: 1 / Applied symmetry - Point group: C2 (2 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 5.0-beta) / Number images used: 88691
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 5.0-beta)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 5.0-beta)
FSC plot (resolution estimation)

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