[English] 日本語
Yorodumi
- EMDB-17677: Human OATP1B1 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-17677
TitleHuman OATP1B1
Map dataE1S-bound Human OATP1B1 with Fab18
Sample
  • Complex: Human OATP1B1
    • Complex: Solute carrier organic anion transporter family member 1B1
      • Protein or peptide: Solute carrier organic anion transporter family member 1B1
    • Complex: Fab18 (variable region)
      • Protein or peptide: Fab18 (heavy chain, variable region)
      • Protein or peptide: Fab18 (light chain, variable region)
  • Ligand: estrone 3-sulfate
  • Ligand: CHOLESTEROL HEMISUCCINATE
Keywordsorganic anion / E1S / E-3-S / estrone-3-sulphate / SLCO1B1 / uptake / drug / transporter / polypeptide / liver / hepatocyte / TRANSPORT PROTEIN
Function / homology
Function and homology information


Defective SLCO1B1 causes hyperbilirubinemia, Rotor type (HBLRR) / Transport of organic anions / sodium-independent organic anion transmembrane transporter activity / sodium-independent organic anion transport / thyroid hormone transmembrane transporter activity / bile acid transmembrane transporter activity / prostaglandin transmembrane transporter activity / organic anion transport / heme catabolic process / Atorvastatin ADME ...Defective SLCO1B1 causes hyperbilirubinemia, Rotor type (HBLRR) / Transport of organic anions / sodium-independent organic anion transmembrane transporter activity / sodium-independent organic anion transport / thyroid hormone transmembrane transporter activity / bile acid transmembrane transporter activity / prostaglandin transmembrane transporter activity / organic anion transport / heme catabolic process / Atorvastatin ADME / organic anion transmembrane transporter activity / bile acid and bile salt transport / Heme degradation / monoatomic ion transport / Recycling of bile acids and salts / xenobiotic metabolic process / basal plasma membrane / basolateral plasma membrane / membrane / plasma membrane
Similarity search - Function
Organic anion transporter polypeptide / Organic Anion Transporter Polypeptide (OATP) family / Kazal-type serine protease inhibitor domain / Kazal domain superfamily / Kazal domain / Kazal domain profile. / Major facilitator superfamily domain / Major facilitator superfamily (MFS) profile. / MFS transporter superfamily
Similarity search - Domain/homology
Solute carrier organic anion transporter family member 1B1
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsCiuta A-D / Nosol K / Kowal J / Mukherjee S / Ramirez AS / Stieger B / Kossiakoff AA / Locher KP
Funding support Switzerland, United States, 2 items
OrganizationGrant numberCountry
Swiss National Science Foundation310030_189111 Switzerland
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM117372 United States
CitationJournal: Nat Commun / Year: 2023
Title: Structure of human drug transporters OATP1B1 and OATP1B3.
Authors: Anca-Denise Ciută / Kamil Nosol / Julia Kowal / Somnath Mukherjee / Ana S Ramírez / Bruno Stieger / Anthony A Kossiakoff / Kaspar P Locher /
Abstract: The organic anion transporting polypeptides OATP1B1 and OATP1B3 are membrane proteins that mediate uptake of drugs into the liver for subsequent conjugation and biliary excretion, a key step in drug ...The organic anion transporting polypeptides OATP1B1 and OATP1B3 are membrane proteins that mediate uptake of drugs into the liver for subsequent conjugation and biliary excretion, a key step in drug elimination from the human body. Polymorphic variants of these transporters can cause reduced drug clearance and adverse drug effects such as statin-induced rhabdomyolysis, and co-administration of OATP substrates can lead to damaging drug-drug interaction. Despite their clinical relevance in drug disposition and pharmacokinetics, the structure and mechanism of OATPs are unknown. Here we present cryo-EM structures of human OATP1B1 and OATP1B3 bound to synthetic Fab fragments and in functionally distinct states. A single estrone-3-sulfate molecule is bound in a pocket located in the C-terminal half of OATP1B1. The shape and chemical nature of the pocket rationalize the preference for diverse organic anions and allow in silico docking of statins. The structure of OATP1B3 is determined in a drug-free state but reveals a bicarbonate molecule bound to the conserved signature motif and a histidine residue that is prevalent in OATPs exhibiting pH-dependent activity.
History
DepositionJun 20, 2023-
Header (metadata) releaseSep 27, 2023-
Map releaseSep 27, 2023-
UpdateMar 20, 2024-
Current statusMar 20, 2024Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_17677.png

Downloads & links

-
Map

FileDownload / File: emd_17677.map.gz / Format: CCP4 / Size: 421.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationE1S-bound Human OATP1B1 with Fab18
Voxel sizeX=Y=Z: 0.51 Å
Density
Contour LevelBy AUTHOR: 0.128
Minimum - Maximum-0.0018009443 - 1.9770203
Average (Standard dev.)0.0009635592 (±0.02181488)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions480480480
Spacing480480480
CellA=B=C: 244.79999 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: E1S-bound Human OATP1B1 with Fab18 (half-map B)

Fileemd_17677_half_map_1.map
AnnotationE1S-bound Human OATP1B1 with Fab18 (half-map B)
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: E1S-bound Human OATP1B1 with Fab18 (half-map A)

Fileemd_17677_half_map_2.map
AnnotationE1S-bound Human OATP1B1 with Fab18 (half-map A)
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Human OATP1B1

EntireName: Human OATP1B1
Components
  • Complex: Human OATP1B1
    • Complex: Solute carrier organic anion transporter family member 1B1
      • Protein or peptide: Solute carrier organic anion transporter family member 1B1
    • Complex: Fab18 (variable region)
      • Protein or peptide: Fab18 (heavy chain, variable region)
      • Protein or peptide: Fab18 (light chain, variable region)
  • Ligand: estrone 3-sulfate
  • Ligand: CHOLESTEROL HEMISUCCINATE

-
Supramolecule #1: Human OATP1B1

SupramoleculeName: Human OATP1B1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Molecular weightTheoretical: 180 KDa

-
Supramolecule #2: Solute carrier organic anion transporter family member 1B1

SupramoleculeName: Solute carrier organic anion transporter family member 1B1
type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

-
Supramolecule #3: Fab18 (variable region)

SupramoleculeName: Fab18 (variable region) / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Solute carrier organic anion transporter family member 1B1

MacromoleculeName: Solute carrier organic anion transporter family member 1B1
type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 76.519438 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MDQNQHLNKT AEAQPSENKK TRYCNGLKMF LAALSLSFIA KTLGAIIMKS SIIHIERRFE ISSSLVGFID GSFEIGNLLV IVFVSYFGS KLHRPKLIGI GCFIMGIGGV LTALPHFFMG YYRYSKETNI NSSENSTSTL STCLINQILS LNRASPEIVG K GCLKESGS ...String:
MDQNQHLNKT AEAQPSENKK TRYCNGLKMF LAALSLSFIA KTLGAIIMKS SIIHIERRFE ISSSLVGFID GSFEIGNLLV IVFVSYFGS KLHRPKLIGI GCFIMGIGGV LTALPHFFMG YYRYSKETNI NSSENSTSTL STCLINQILS LNRASPEIVG K GCLKESGS YMWIYVFMGN MLRGIGETPI VPLGLSYIDD FAKEGHSSLY LGILNAIAMI GPIIGFTLGS LFSKMYVDIG YV DLSTIRI TPTDSRWVGA WWLNFLVSGL FSIISSIPFF FLPQTPNKPQ KERKASLSLH VLETNDEKDQ TANLTNQGKN ITK NVTGFF QSFKSILTNP LYVMFVLLTL LQVSSYIGAF TYVFKYVEQQ YGQPSSKANI LLGVITIPIF ASGMFLGGYI IKKF KLNTV GIAKFSCFTA VMSLSFYLLY FFILCENKSV AGLTMTYDGN NPVTSHRDVP LSYCNSDCNC DESQWEPVCG NNGIT YISP CLAGCKSSSG NKKPIVFYNC SCLEVTGLQN RNYSAHLGEC PRDDACTRKF YFFVAIQVLN LFFSALGGTS HVMLIV KIV QPELKSLALG FHSMVIRALG GILAPIYFGA LIDTTCIKWS TNNCGTRGSC RTYNSTSFSR VYLGLSSMLR VSSLVLY II LIYAMKKKYQ EKDINASENG SVMDEANLES LNKNKHFVPS AGADSETHC

UniProtKB: Solute carrier organic anion transporter family member 1B1

-
Macromolecule #2: Fab18 (heavy chain, variable region)

MacromoleculeName: Fab18 (heavy chain, variable region) / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 24.374008 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: EISEVQLVES GGGLVQPGGS LRLSCAASGF NFSSSSIHWV RQAPGKGLEW VASISSSSGS TSYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARYGWGGPWY YWLRDSRSGI DYWGQGTLVT VSSASTKGPS VSGGTAALGC LVKDYFPEPV T VSWNSGAL ...String:
EISEVQLVES GGGLVQPGGS LRLSCAASGF NFSSSSIHWV RQAPGKGLEW VASISSSSGS TSYADSVKGR FTISADTSKN TAYLQMNSL RAEDTAVYYC ARYGWGGPWY YWLRDSRSGI DYWGQGTLVT VSSASTKGPS VSGGTAALGC LVKDYFPEPV T VSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK KVEPKSCDKT HT

-
Macromolecule #3: Fab18 (light chain, variable region)

MacromoleculeName: Fab18 (light chain, variable region) / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.258783 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQSSSSLITF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String:
SDIQMTQSPS SLSASVGDRV TITCRASQSV SSAVAWYQQK PGKAPKLLIY SASSLYSGVP SRFSGSRSGT DFTLTISSLQ PEDFATYYC QQSSSSLITF GQGTKVEIKR TVAAPSVFIF PPSDSQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC

-
Macromolecule #4: estrone 3-sulfate

MacromoleculeName: estrone 3-sulfate / type: ligand / ID: 4 / Number of copies: 1 / Formula: FY5
Molecular weightTheoretical: 350.429 Da
Chemical component information

ChemComp-FY5:
estrone 3-sulfate / medication, hormone*YM / Estrone sulfate

-
Macromolecule #5: CHOLESTEROL HEMISUCCINATE

MacromoleculeName: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 5 / Number of copies: 1 / Formula: Y01
Molecular weightTheoretical: 486.726 Da
Chemical component information

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration0.22 mg/mL
BufferpH: 7.4
VitrificationCryogen name: ETHANE-PROPANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.6 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.5 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: NONE
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 104547
FSC plot (resolution estimation)

+
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