[English] 日本語
Yorodumi
- PDB-9mjo: Cryo-EM structure of human NBCn2 bound to Carbonate -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9mjo
TitleCryo-EM structure of human NBCn2 bound to Carbonate
ComponentsSodium-driven chloride bicarbonate exchanger
KeywordsMEMBRANE PROTEIN / Transmembrane / Transport Protein
Function / homology
Function and homology information


sodium,bicarbonate:chloride antiporter activity / CA3 pyramidal cell dendrite / sodium:bicarbonate symporter activity / basal dendrite / Bicarbonate transporters / solute:inorganic anion antiporter activity / regulation of short-term neuronal synaptic plasticity / bicarbonate transport / apical dendrite / chloride transport ...sodium,bicarbonate:chloride antiporter activity / CA3 pyramidal cell dendrite / sodium:bicarbonate symporter activity / basal dendrite / Bicarbonate transporters / solute:inorganic anion antiporter activity / regulation of short-term neuronal synaptic plasticity / bicarbonate transport / apical dendrite / chloride transport / visual perception / somatodendritic compartment / axon terminus / regulation of intracellular pH / GABA-ergic synapse / transmembrane transport / basolateral plasma membrane / perikaryon / postsynapse / apical plasma membrane / neuronal cell body / dendrite / synapse / membrane / plasma membrane
Similarity search - Function
Sodium bicarbonate cotransporter / Band 3 cytoplasmic domain / Band 3 cytoplasmic domain / Phosphotransferase/anion transporter / Bicarbonate transporter, eukaryotic / Bicarbonate transporter-like, transmembrane domain / HCO3- transporter integral membrane domain
Similarity search - Domain/homology
CHOLESTEROL / CARBONATE ION / Sodium-driven chloride bicarbonate exchanger
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.45 Å
AuthorsYang, S. / Capper, M.J. / Zilberg, G. / Warren, A.L. / Wacker, D.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35 GM133504 United States
CitationJournal: Nat Commun / Year: 2026
Title: Structural insights enable drug discovery for the neuronal NBCn2 carbonate transporter.
Authors: Shifan Yang / Yihan Zhao / Sezen Vatansever / Gregory Zilberg / Michael J Capper / Jinglong Zhang / Joshua Stamos / Keino Hutchinson / Audrey L Warren / Alexander C Stone / Anwar Abbassi / ...Authors: Shifan Yang / Yihan Zhao / Sezen Vatansever / Gregory Zilberg / Michael J Capper / Jinglong Zhang / Joshua Stamos / Keino Hutchinson / Audrey L Warren / Alexander C Stone / Anwar Abbassi / Eric Purisic / Lap Ho / Aiqun Li / Jinye Dai / Avner Schlessinger / Bin Zhang / Daniel Wacker /
Abstract: NBCn2 (SLC4A10), a member of the SLC4 solute carrier (SLC) family, is a sodium-dependent (bi)carbonate transporter that regulates acid extrusion in various brain regions. Mutations in NBCn2 cause ...NBCn2 (SLC4A10), a member of the SLC4 solute carrier (SLC) family, is a sodium-dependent (bi)carbonate transporter that regulates acid extrusion in various brain regions. Mutations in NBCn2 cause severe neurodevelopmental disorders in humans, and knock out studies suggest that its role in regulating neuronal excitability could hold therapeutic potential for seizure disorders such as epilepsy. Despite its physiological importance, NBCn2's molecular mechanisms remain largely unknown, and there is limited availability of tool compounds to further probe its role in health and disease. Combining cryoEM with computational docking and simulation studies, we herein elucidate NBCn2's molecular architecture and substrate binding mechanisms on the atomic scale. Via structure-based drug discovery we further identify a compound series that inhibits NBCn2-mediated transport, and characterize its inhibitory mechanisms via cryoEM. Lastly, we showcase the potential of this compound series to template useful probes by demonstrating pharmacological activity both in primary culture as well as brain slices.
History
DepositionDec 16, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 5, 2026Provider: repository / Type: Initial release
Revision 1.0Aug 5, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Aug 5, 2026Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Aug 5, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Aug 5, 2026Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Aug 5, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Aug 5, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Sep 9, 2026Group: Data collection / Database references / Category: citation / em_admin
Item: _citation.journal_volume / _citation.pdbx_database_id_PubMed ..._citation.journal_volume / _citation.pdbx_database_id_PubMed / _citation.title / _em_admin.last_update
Revision 1.1Sep 9, 2026Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Database references / Experimental summary / Data content type: EM metadata / EM metadata / Category: citation / em_admin
Data content type: EM metadata / EM metadata ...EM metadata / EM metadata / EM metadata / EM metadata
Item: _citation.journal_volume / _citation.pdbx_database_id_PubMed ..._citation.journal_volume / _citation.pdbx_database_id_PubMed / _citation.title / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
B: Sodium-driven chloride bicarbonate exchanger
A: Sodium-driven chloride bicarbonate exchanger
hetero molecules


Theoretical massNumber of molelcules
Total (without water)225,28816
Polymers221,9832
Non-polymers3,30514
Water1086
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

#1: Protein Sodium-driven chloride bicarbonate exchanger / Solute carrier family 4 member 10


Mass: 110991.359 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SLC4A10, NBCN2, NCBE / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q6U841
#2: Chemical
ChemComp-CLR / CHOLESTEROL


Mass: 386.654 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C27H46O
#3: Chemical ChemComp-CO3 / CARBONATE ION


Mass: 60.009 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: CO3
#4: Chemical
ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Na
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 6 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: Dimeric NBCn2 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Molecular weightValue: 0.22 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm) / Strain: Sf9 / Plasmid: pFB
Buffer solutionpH: 7.5
Buffer component
IDConc.NameBuffer-ID
120 mMHEPES1
2150 mMSodium Chloride1
30.0011 % (w/v)LMNG1
40.00011 % (w/v)CHS1
50.00025 % (w/v)GDN1
6100 mMSodium Bicarbonate1
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: LEICA EM GP / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 285 K / Details: Blot force 3 for 3 seconds

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

EM softwareName: PHENIX / Version: 1.19.2_4158 / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 1368863
SymmetryPoint symmetry: C2 (2 fold cyclic)
3D reconstructionResolution: 2.45 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 291402 / Symmetry type: POINT
RefinementHighest resolution: 2.45 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0038866
ELECTRON MICROSCOPYf_angle_d0.46612092
ELECTRON MICROSCOPYf_dihedral_angle_d6.7741344
ELECTRON MICROSCOPYf_chiral_restr0.041456
ELECTRON MICROSCOPYf_plane_restr0.0051418

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more