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- EMDB-46005: Outward-facing Atorvastatin-bound OATP1B1 with sybody Sb5 -

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Basic information

Entry
Database: EMDB / ID: EMD-46005
TitleOutward-facing Atorvastatin-bound OATP1B1 with sybody Sb5
Map data
Sample
  • Complex: Outward-facing atorvastatin-bound OATP1B1 with Sybody 5
    • Protein or peptide: Solute carrier organic anion transporter family member 1B1
    • Protein or peptide: Sybody 5
  • Ligand: 7-[2-(4-FLUORO-PHENYL)-5-ISOPROPYL-3-PHENYL-4-PHENYLCARBAMOYL-PYRROL-1-YL]- 3,5-DIHYDROXY-HEPTANOIC ACID
Keywordssolute carrier / sybody / membrane protein / drug-drug interactions / TRANSPORT PROTEIN
Function / homology
Function and homology information


Defective SLCO1B1 causes hyperbilirubinemia, Rotor type (HBLRR) / Transport of organic anions / sodium-independent organic anion transport / sodium-independent organic anion transmembrane transporter activity / thyroid hormone transmembrane transporter activity / prostaglandin transmembrane transporter activity / organic anion transport / heme catabolic process / organic anion transmembrane transporter activity / Atorvastatin ADME ...Defective SLCO1B1 causes hyperbilirubinemia, Rotor type (HBLRR) / Transport of organic anions / sodium-independent organic anion transport / sodium-independent organic anion transmembrane transporter activity / thyroid hormone transmembrane transporter activity / prostaglandin transmembrane transporter activity / organic anion transport / heme catabolic process / organic anion transmembrane transporter activity / Atorvastatin ADME / bile acid transmembrane transporter activity / Heme degradation / bile acid and bile salt transport / Recycling of bile acids and salts / monoatomic ion transport / 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) / synthetic construct (others)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsSung MW / Lees JA / Han S
Funding support United States, 1 items
OrganizationGrant numberCountry
Other private United States
CitationJournal: J Biol Chem / Year: 2025
Title: Cyclosporine A sterically inhibits statin transport by solute carrier OATP1B1.
Authors: Min Woo Sung / Kuan Hu / Lea M Hurlimann / Joshua A Lees / Kimberly F Fennell / Mark A West / Chester Costales / Amilcar David Rodrigues / Iwan Zimmermann / Roger J P Dawson / Shenping Liu / Seungil Han /
Abstract: Members of the Organic Anion Transporter Polypeptides (OATP) are integral membrane proteins responsible for facilitating the transport of organic anions across the cell membrane. OATP1B1 (SLCO1B1), ...Members of the Organic Anion Transporter Polypeptides (OATP) are integral membrane proteins responsible for facilitating the transport of organic anions across the cell membrane. OATP1B1 (SLCO1B1), the prototypic OATP family member, is the most abundant uptake transporter in the liver and a key mediator of the hepatic uptake and clearance of numerous endogenous and xenobiotic compounds. It serves as a locus of important drug-drug interactions, such as those between statins and cyclosporine A, and carries the potential to enable liver-targeting therapeutics. In this study, we report cryo-EM structures of OATP1B1 and its complexes with one of its statin substrates, atorvastatin, and an inhibitor, cyclosporine A. This structural analysis has yielded insights into the mechanisms underlying the OATP1B1-mediated transport of statins and the inhibitory effect of cyclosporine A. These findings contribute to a better understanding of the molecular processes involved in drug transport and offer potential avenues for the development of targeted medications for liver-related conditions.
History
DepositionAug 1, 2024-
Header (metadata) releaseApr 16, 2025-
Map releaseApr 16, 2025-
UpdateMay 14, 2025-
Current statusMay 14, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_46005.png

Downloads & links

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Map

FileDownload / File: emd_46005.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.1 Å/pix.
x 240 pix.
= 263.76 Å		1.1 Å/pix.
x 240 pix.
= 263.76 Å		1.1 Å/pix.
x 240 pix.
= 263.76 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.099 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.2
Minimum - Maximum-1.1273446 - 1.5940094
Average (Standard dev.)0.00010006254 (±0.026446316)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions240240240
Spacing240240240
CellA=B=C: 263.76 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_46005_half_map_1.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

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Histogram (log scale)

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Half map: #2

Fileemd_46005_half_map_2.map
Projections & Slices
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Histogram (log scale)

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Sample components

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Entire : Outward-facing atorvastatin-bound OATP1B1 with Sybody 5

EntireName: Outward-facing atorvastatin-bound OATP1B1 with Sybody 5
Components
  • Complex: Outward-facing atorvastatin-bound OATP1B1 with Sybody 5
    • Protein or peptide: Solute carrier organic anion transporter family member 1B1
    • Protein or peptide: Sybody 5
  • Ligand: 7-[2-(4-FLUORO-PHENYL)-5-ISOPROPYL-3-PHENYL-4-PHENYLCARBAMOYL-PYRROL-1-YL]- 3,5-DIHYDROXY-HEPTANOIC ACID

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Supramolecule #1: Outward-facing atorvastatin-bound OATP1B1 with Sybody 5

SupramoleculeName: Outward-facing atorvastatin-bound OATP1B1 with Sybody 5
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

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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: 79.880977 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MHHHHHHHHH HDYKDDDDKE NLYFQGMDQN QHLNKTAEAQ PSENKKTRYC NGLKMFLAAL SLSFIAKTLG AIIMKSSIIH IERRFEISS SLVGFIDGSF EIGNLLVIVF VSYFGSKLHR PKLIGIGCFI MGIGGVLTAL PHFFMGYYRY SKETNINSSE N STSTLSTC ...String:
MHHHHHHHHH HDYKDDDDKE NLYFQGMDQN QHLNKTAEAQ PSENKKTRYC NGLKMFLAAL SLSFIAKTLG AIIMKSSIIH IERRFEISS SLVGFIDGSF EIGNLLVIVF VSYFGSKLHR PKLIGIGCFI MGIGGVLTAL PHFFMGYYRY SKETNINSSE N STSTLSTC LINQILSLNR ASPEIVGKGC LKESGSYMWI YVFMGNMLRG IGETPIVPLG LSYIDDFAKE GHSSLYLGIL NA IAMIGPI IGFTLGSLFS KMYVDIGYVD LSTIRITPTD SRWVGAWWLN FLVSGLFSII SSIPFFFLPQ TPNKPQKERK ASL SLHVLE TNDEKDQTAN LTNQGKNITK NVTGFFQSFK SILTNPLYVM FVLLTLLQVS SYIGAFTYVF KYVEQQYGQP SSKA NILLG VITIPIFASG MFLGGYIIKK FKLNTVGIAK FSCFTAVMSL SFYLLYFFIL CENKSVAGLT MTYDGNNPVT SHRDV PLSY CNSDCNCDES QWEPVCGNNG ITYISPCLAG CKSSSGNKKP IVFYNCSCLE VTGLQNRNYS AHLGECPRDD ACTRKF YFF VAIQVLNLFF SALGGTSHVM LIVKIVQPEL KSLALGFHSM VIRALGGILA PIYFGALIDT TCIKWSTNNC GTRGSCR TY NSTSFSRVYL GLSSMLRVSS LVLYIILIYA MKKKYQEKDI NASENGSVMD EANLESLNKN KHFVPSAGAD SETHC

UniProtKB: Solute carrier organic anion transporter family member 1B1

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Macromolecule #2: Sybody 5

MacromoleculeName: Sybody 5 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: synthetic construct (others)
Molecular weightTheoretical: 15.88551 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
GSSSQVQLVE SGGGLVQAGG SLRLSCAASG FPVNLSYMHW YRQAPGKERE WVAAISSWGW HTEYADSVKG RFTISRDNAK NTVYLQMNS LKPEDTAVYY CHVRVGRSYF GQGTQVSVSA GRAGEQKLIS EEDLNSAVDH HHHHH

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Macromolecule #3: 7-[2-(4-FLUORO-PHENYL)-5-ISOPROPYL-3-PHENYL-4-PHENYLCARBAMOYL-PYR...

MacromoleculeName: 7-[2-(4-FLUORO-PHENYL)-5-ISOPROPYL-3-PHENYL-4-PHENYLCARBAMOYL-PYRROL-1-YL]- 3,5-DIHYDROXY-HEPTANOIC ACID
type: ligand / ID: 3 / Number of copies: 1 / Formula: 117
Molecular weightTheoretical: 558.64 Da
Chemical component information

ChemComp-117:
7-[2-(4-FLUORO-PHENYL)-5-ISOPROPYL-3-PHENYL-4-PHENYLCARBAMOYL-PYRROL-1-YL]- 3,5-DIHYDROXY-HEPTANOIC ACID / medication*YM

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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

BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: TFS FALCON 4i (4k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.6 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 127971
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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