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- EMDB-30790: Cryo-EM structure of the human ABCB6 (coproporphyrin III-bound) -
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Open data
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Basic information
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Title | Cryo-EM structure of the human ABCB6 (coproporphyrin III-bound) | |||||||||||||||
![]() | generated from non-uniform refinement in cryosparc | |||||||||||||||
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![]() | ABCB6 / heme transporter / MEMBRANE PROTEIN | |||||||||||||||
Function / homology | ![]() cellular detoxification of cadmium ion / Defective ABCB6 causes MCOPCB7 / Mitochondrial ABC transporters / tetrapyrrole metabolic process / ABC-type heme transporter / porphyrin-containing compound metabolic process / heme transport / tetrapyrrole binding / heme metabolic process / porphyrin-containing compound biosynthetic process ...cellular detoxification of cadmium ion / Defective ABCB6 causes MCOPCB7 / Mitochondrial ABC transporters / tetrapyrrole metabolic process / ABC-type heme transporter / porphyrin-containing compound metabolic process / heme transport / tetrapyrrole binding / heme metabolic process / porphyrin-containing compound biosynthetic process / melanosome assembly / heme transmembrane transport / ABC-type heme transporter activity / melanosome membrane / multivesicular body membrane / mitochondrial envelope / endolysosome membrane / 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 / Golgi membrane / lysosomal 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 | ![]() | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||||||||
![]() | Kim S / Lee SS | |||||||||||||||
Funding support | ![]()
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![]() | ![]() 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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 141.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 13 KB 13 KB | Display Display | ![]() |
Images | ![]() | 30.6 KB | ||
Filedesc metadata | ![]() | 5.9 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7dnyMC ![]() 7dnzC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | generated from non-uniform refinement in cryosparc | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.656 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : ABCB6
Entire | Name: ABCB6 |
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Components |
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-Supramolecule #1: ABCB6
Supramolecule | Name: ABCB6 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: ATP-binding cassette sub-family B member 6, mitochondrial
Macromolecule | Name: ATP-binding cassette sub-family B member 6, mitochondrial type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 93.974172 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MVTVGNYCEA EGPVGPAWMQ DGLSPCFFFT LVPSTRMALG TLALVLALPC RRRERPAGAD SLSWGAGPRI SPYVLQLLLA TLQAALPLA GLAGRVGTAR GAPLPSYLLL ASVLESLAGA CGLWLLVVER SQARQRLAMG IWIKFRHSPG LLLLWTVAFA A ENLALVSW ...String: MVTVGNYCEA EGPVGPAWMQ DGLSPCFFFT LVPSTRMALG TLALVLALPC RRRERPAGAD SLSWGAGPRI SPYVLQLLLA TLQAALPLA GLAGRVGTAR GAPLPSYLLL ASVLESLAGA CGLWLLVVER SQARQRLAMG IWIKFRHSPG LLLLWTVAFA A ENLALVSW NSPQWWWARA DLGQQVQFSL WVLRYVVSGG LFVLGLWAPG LRPQSYTLQV HEEDQDVERS QVRSAAQQST WR DFGRKLR LLSGYLWPRG SPALQLVVLI CLGLMGLERA LNVLVPIFYR NIVNLLTEKA PWNSLAWTVT SYVFLKFLQG GGT GSTGFV SNLRTFLWIR VQQFTSRRVE LLIFSHLHEL SLRWHLGRRT GEVLRIADRG TSSVTGLLSY LVFNVIPTLA DIII GIIYF SMFFNAWFGL IVFLCMSLYL TLTIVVTEWR TKFRRAMNTQ ENATRARAVD SLLNFETVKY YNAESYEVER YREAI IKYQ GLEWKSSASL VLLNQTQNLV IGLGLLAGSL LCAYFVTEQK LQVGDYVLFG TYIIQLYMPL NWFGTYYRMI QTNFID MEN MFDLLKEETE VKDLPGAGPL RFQKGRIEFE NVHFSYADGR ETLQDVSFTV MPGQTLALVG PSGAGKSTIL RLLFRFY DI SSGCIRIDGQ DISQVTQASL RSHIGVVPQD TVLFNDTIAD NIRYGRVTAG NDEVEAAAQA AGIHDAIMAF PEGYRTQV G ERGLKLSGGE KQRVAIARTI LKAPGIILLD EATSALDTSN ERAIQASLAK VCANRTTIVV AHRLSTVVNA DQILVIKDG CIVERGRHEA LLSRGGVYAD MWQLQQGQEE TSEDTKPQTM ER UniProtKB: ATP-binding cassette sub-family B member 6 |
-Macromolecule #2: CHOLESTEROL HEMISUCCINATE
Macromolecule | Name: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 2 / Number of copies: 5 / Formula: Y01 |
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Molecular weight | Theoretical: 486.726 Da |
Chemical component information | ![]() ChemComp-Y01: |
-Macromolecule #3: coproporphyrin III
Macromolecule | Name: coproporphyrin III / type: ligand / ID: 3 / Number of copies: 1 / Formula: HT9 |
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Molecular weight | Theoretical: 654.709 Da |
Chemical component information | ![]() ChemComp-HT9: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 6 mg/mL |
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Buffer | pH: 7 / Component - Concentration: 200.0 mM / Component - Formula: NaCl / Component - Name: sodium chloride |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV |
Details | This sample was monodisperse. |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: Details: We also used PDB ID 3NH6 as a startup model. |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 108637 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 3.1) |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 2.15.0) |
-Atomic model buiding 1
Refinement | Protocol: RIGID BODY FIT |
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Output model | ![]() PDB-7dny: |