+Open data
-Basic information
Entry | Database: PDB / ID: 7dnz | |||||||||||||||
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Title | Cryo-EM structure of the human ABCB6 (Hemin and GSH-bound) | |||||||||||||||
Components | ATP-binding cassette sub-family B member 6, mitochondrial | |||||||||||||||
Keywords | MEMBRANE PROTEIN / ABCB6 / heme transporter | |||||||||||||||
Function / homology | Function and homology information Defective ABCB6 causes MCOPCB7 / cellular detoxification of cadmium ion / Mitochondrial ABC transporters / tetrapyrrole metabolic process / ABC-type heme transporter / porphyrin-containing compound metabolic process / tetrapyrrole binding / heme transport / heme metabolic process / porphyrin-containing compound biosynthetic process ...Defective ABCB6 causes MCOPCB7 / cellular detoxification of cadmium ion / Mitochondrial ABC transporters / tetrapyrrole metabolic process / ABC-type heme transporter / porphyrin-containing compound metabolic process / tetrapyrrole binding / heme transport / heme metabolic process / porphyrin-containing compound biosynthetic process / melanosome assembly / heme transmembrane transport / ABC-type heme transporter activity / melanosome membrane / multivesicular body membrane / endolysosome membrane / mitochondrial envelope / vacuolar membrane / skin development / efflux transmembrane transporter activity / intracellular copper ion homeostasis / ABC-type transporter activity / ATP-binding cassette (ABC) transporter complex / brain development / transmembrane transport / early endosome membrane / intracellular iron ion homeostasis / mitochondrial outer membrane / endosome / lysosomal membrane / Golgi membrane / heme binding / endoplasmic reticulum membrane / Golgi apparatus / endoplasmic reticulum / ATP hydrolysis activity / mitochondrion / extracellular exosome / nucleoplasm / ATP binding / plasma membrane / cytosol Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||||||||
Authors | Kim, S. / Lee, S.S. / Park, J.G. / Kim, J.W. / Kim, S. / Kim, N.J. / Hong, S. / Kang, J.Y. / Jin, M.S. | |||||||||||||||
Funding support | Korea, Republic Of, 4items
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Citation | Journal: Mol Cells / Year: 2022 Title: Structural Insights into Porphyrin Recognition by the Human ATP-Binding Cassette Transporter ABCB6. Authors: Songwon Kim / Sang Soo Lee / Jun Gyou Park / Ji Won Kim / Seulgi Ju / Seung Hun Choi / Subin Kim / Na Jin Kim / Semi Hong / Jin Young Kang / Mi Sun Jin / Abstract: Human ABCB6 is an ATP-binding cassette transporter that regulates heme biosynthesis by translocating various porphyrins from the cytoplasm into the mitochondria. Here we report the cryo-electron ...Human ABCB6 is an ATP-binding cassette transporter that regulates heme biosynthesis by translocating various porphyrins from the cytoplasm into the mitochondria. Here we report the cryo-electron microscopy (cryo-EM) structures of human ABCB6 with its substrates, coproporphyrin III (CPIII) and hemin, at 3.5 and 3.7 Å resolution, respectively. Metalfree porphyrin CPIII binds to ABCB6 within the central cavity, where its propionic acids form hydrogen bonds with the highly conserved Y550. The resulting structure has an overall fold similar to the inward-facing apo structure, but the two nucleotide-binding domains (NBDs) are slightly closer to each other. In contrast, when ABCB6 binds a metal-centered porphyrin hemin in complex with two glutathione molecules (1 hemin: 2 glutathione), the two NBDs end up much closer together, aligning them to bind and hydrolyze ATP more efficiently. In our structures, a glycine-rich and highly flexible "bulge" loop on TM helix 7 undergoes significant conformational changes associated with substrate binding. Our findings suggest that ABCB6 utilizes at least two distinct mechanisms to fine-tune substrate specificity and transport efficiency. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7dnz.cif.gz | 230.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7dnz.ent.gz | 180 KB | Display | PDB format |
PDBx/mmJSON format | 7dnz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7dnz_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 7dnz_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 7dnz_validation.xml.gz | 39.4 KB | Display | |
Data in CIF | 7dnz_validation.cif.gz | 58.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dn/7dnz ftp://data.pdbj.org/pub/pdb/validation_reports/dn/7dnz | HTTPS FTP |
-Related structure data
Related structure data | 30791MC 7dnyC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 93974.172 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ABCB6, MTABC3, PRP, UMAT / Cell line (production host): BTI-Tn-5B1-4 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9NP58 #2: Chemical | ChemComp-GSH / #3: Chemical | ChemComp-Y01 / #4: Chemical | ChemComp-HEM / | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: ABCB6 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | ||||||||||||||||||||
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Source (natural) | Organism: Homo sapiens (human) | ||||||||||||||||||||
Source (recombinant) | Organism: Trichoplusia ni (cabbage looper) / Cell: BTI-Tn-5B1-4 | ||||||||||||||||||||
Buffer solution | pH: 7 | ||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 6 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: This sample was monodisperse. | ||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2600 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 283866 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT | ||||||||||||||||||||||||
Refine LS restraints |
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