[English] 日本語
Yorodumi
- PDB-6d7o: Crystal Structure of Rat TRPV6* in complex with 2-Aminoethoxydiph... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6d7o
TitleCrystal Structure of Rat TRPV6* in complex with 2-Aminoethoxydiphenyl borate (2-APB)
ComponentsTransient receptor potential cation channel subfamily V member 6
Keywordsmembrane protein/inhibitor / Ion channels / transporter / calcium channel / epithelial calcium channel / MEMBRANE PROTEIN / membrane protein-inhibitor complex
Function / homology
Function and homology information


parathyroid hormone secretion / TRP channels / calcium-activated cation channel activity / calcium ion import / calcium ion import across plasma membrane / calcium ion homeostasis / calcium channel complex / calcium ion transmembrane transport / calcium channel activity / response to calcium ion ...parathyroid hormone secretion / TRP channels / calcium-activated cation channel activity / calcium ion import / calcium ion import across plasma membrane / calcium ion homeostasis / calcium channel complex / calcium ion transmembrane transport / calcium channel activity / response to calcium ion / calcium ion transport / protein homotetramerization / calmodulin binding / apical plasma membrane / metal ion binding / identical protein binding / plasma membrane
Similarity search - Function
Transient receptor potential cation channel subfamily V member 6 / Transient receptor potential cation channel subfamily V member 5/6 / Ankyrin repeats (many copies) / Transient receptor potential cation channel subfamily V / Ankyrin repeats (3 copies) / Ankyrin repeat profile. / Ankyrin repeat region circular profile. / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily ...Transient receptor potential cation channel subfamily V member 6 / Transient receptor potential cation channel subfamily V member 5/6 / Ankyrin repeats (many copies) / Transient receptor potential cation channel subfamily V / Ankyrin repeats (3 copies) / Ankyrin repeat profile. / Ankyrin repeat region circular profile. / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily / Ion transport domain / Ion transport protein
Similarity search - Domain/homology
Chem-DTB / 2-aminoethyl diphenylborinate / Transient receptor potential cation channel subfamily V member 6
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.45 Å
AuthorsSingh, A.K. / Saotome, K. / McGoldrick, L.L. / Sobolevsky, A.I.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)1R01CA206573-01A1 United States
CitationJournal: Nat Commun / Year: 2018
Title: Structural bases of TRP channel TRPV6 allosteric modulation by 2-APB.
Authors: Appu K Singh / Kei Saotome / Luke L McGoldrick / Alexander I Sobolevsky /
Abstract: Transient receptor potential (TRP) channels are involved in various physiological processes, including sensory transduction. The TRP channel TRPV6 mediates calcium uptake in epithelia and its ...Transient receptor potential (TRP) channels are involved in various physiological processes, including sensory transduction. The TRP channel TRPV6 mediates calcium uptake in epithelia and its expression is dramatically increased in numerous types of cancer. TRPV6 inhibitors suppress tumor growth, but the molecular mechanism of inhibition remains unknown. Here, we present crystal and cryo-EM structures of human and rat TRPV6 bound to 2-aminoethoxydiphenyl borate (2-APB), a TRPV6 inhibitor and modulator of numerous TRP channels. 2-APB binds to TRPV6 in a pocket formed by the cytoplasmic half of the S1-S4 transmembrane helix bundle. Comparing human wild-type and high-affinity mutant Y467A structures, we show that 2-APB induces TRPV6 channel closure by modulating protein-lipid interactions. Mutagenesis and functional analyses suggest that the identified 2-APB binding site might be present in other members of vanilloid subfamily TRP channels. Our findings reveal a mechanism of ion channel allosteric modulation that can be exploited for therapeutic design.
History
DepositionApr 25, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 18, 2018Provider: repository / Type: Initial release
Revision 1.1Sep 18, 2019Group: Data collection / Category: reflns / reflns_shell
Item: _reflns.pdbx_Rrim_I_all / _reflns_shell.pdbx_Rrim_I_all
Revision 1.2Dec 18, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3Oct 4, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Transient receptor potential cation channel subfamily V member 6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)77,6134
Polymers77,1331
Non-polymers4793
Water0
1
A: Transient receptor potential cation channel subfamily V member 6
hetero molecules

A: Transient receptor potential cation channel subfamily V member 6
hetero molecules

A: Transient receptor potential cation channel subfamily V member 6
hetero molecules

A: Transient receptor potential cation channel subfamily V member 6
hetero molecules


Theoretical massNumber of molelcules
Total (without water)310,45216
Polymers308,5344
Non-polymers1,91812
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_455-x-1,-y,z1
crystal symmetry operation3_455-y-1/2,x+1/2,z1
crystal symmetry operation4_445y-1/2,-x-1/2,z1
Buried area29900 Å2
ΔGint-279 kcal/mol
Surface area106950 Å2
MethodPISA
Unit cell
Length a, b, c (Å)145.384, 145.384, 116.162
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number90
Space group name H-MP4212
Components on special symmetry positions
IDModelComponents
11A-701-

CA

-
Components

#1: Protein Transient receptor potential cation channel subfamily V member 6 / TrpV6 / Calcium transport protein 1 / CaT1 / Epithelial calcium channel 2 / ECaC2


Mass: 77133.492 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Trpv6 / Production host: Homo sapiens (human) / References: UniProt: Q9R186
#2: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Ca
#3: Chemical ChemComp-FZ4 / 2-aminoethyl diphenylborinate / 2-Aminoethoxydiphenyl borate


Mass: 225.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C14H16BNO
#4: Chemical ChemComp-DTB / 6-(5-METHYL-2-OXO-IMIDAZOLIDIN-4-YL)-HEXANOIC ACID / D-DESTHIOBIOTIN


Mass: 214.262 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H18N2O3

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 4 Å3/Da / Density % sol: 69.27 %
Crystal growTemperature: 293 K / Method: vapor diffusion / pH: 8
Details: 20-24% PEG 350 MME, 50 mM NaCl, and 50 mM Tris-HCl pH 8.0-8.5
PH range: 8.0-8.5

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-C / Wavelength: 0.9791 Å
DetectorType: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Sep 7, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9791 Å / Relative weight: 1
ReflectionResolution: 3.4→50 Å / Num. obs: 16642 / % possible obs: 94.92 % / Observed criterion σ(I): 1.02 / Redundancy: 8.5 % / CC1/2: 1 / Rrim(I) all: 0.13 / Net I/av σ(I): 11.44 / Net I/σ(I): 11.44
Reflection shellResolution: 3.4→3.6 Å / Redundancy: 6.7 % / Num. unique obs: 1434 / Rrim(I) all: 1.409 / % possible all: 93.3

-
Processing

Software
NameVersionClassification
PHENIX(1.12_2829: ???)refinement
XDSdata reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5WO7
Resolution: 3.45→47.005 Å / SU ML: 0.58 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 37.15 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.3156 817 5 %
Rwork0.2846 --
obs0.2862 16350 96.49 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 3.45→47.005 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4725 0 33 0 4758
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0024880
X-RAY DIFFRACTIONf_angle_d0.5886624
X-RAY DIFFRACTIONf_dihedral_angle_d13.2512886
X-RAY DIFFRACTIONf_chiral_restr0.037752
X-RAY DIFFRACTIONf_plane_restr0.004835
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.4503-3.66640.4121330.37612552X-RAY DIFFRACTION98
3.6664-3.94930.41791360.34592582X-RAY DIFFRACTION98
3.9493-4.34650.31871360.28942587X-RAY DIFFRACTION98
4.3465-4.97480.3061350.27362566X-RAY DIFFRACTION96
4.9748-6.26540.29681350.29542565X-RAY DIFFRACTION95
6.2654-47.00910.2981420.2612681X-RAY DIFFRACTION94

+
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