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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-23409 | |||||||||
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Title | Structure of ATP-free human ABCA4 | |||||||||
![]() | Structure of ATP-free human ABCA4 | |||||||||
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Function / homology | ![]() rod photoreceptor disc membrane / flippase activity / N-retinylidene-phosphatidylethanolamine flippase activity / all-trans retinal binding / phospholipid transfer to membrane / retinol transmembrane transporter activity / phospholipid transporter activity / 11-cis retinal binding / retinal metabolic process / ATPase-coupled intramembrane lipid transporter activity ...rod photoreceptor disc membrane / flippase activity / N-retinylidene-phosphatidylethanolamine flippase activity / all-trans retinal binding / phospholipid transfer to membrane / retinol transmembrane transporter activity / phospholipid transporter activity / 11-cis retinal binding / retinal metabolic process / ATPase-coupled intramembrane lipid transporter activity / phosphatidylethanolamine flippase activity / phototransduction, visible light / retinoid binding / photoreceptor cell maintenance / P-type phospholipid transporter / lipid transport / phospholipid translocation / retinoid metabolic process / Retinoid cycle disease events / The canonical retinoid cycle in rods (twilight vision) / photoreceptor outer segment / ATPase-coupled transmembrane transporter activity / ABC-type transporter activity / visual perception / ABC-family proteins mediated transport / transmembrane transport / photoreceptor disc membrane / cytoplasmic vesicle / intracellular membrane-bounded organelle / GTPase activity / endoplasmic reticulum / ATP hydrolysis activity / ATP binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.27 Å | |||||||||
![]() | Liu F / Lee J / Chen J | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular structures of the eukaryotic retinal importer ABCA4. Authors: Fangyu Liu / James Lee / Jue Chen / ![]() Abstract: The ATP-binding cassette (ABC) transporter family contains thousands of members with diverse functions. Movement of the substrate, powered by ATP hydrolysis, can be outward (export) or inward (import) ...The ATP-binding cassette (ABC) transporter family contains thousands of members with diverse functions. Movement of the substrate, powered by ATP hydrolysis, can be outward (export) or inward (import). ABCA4 is a eukaryotic importer transporting retinal to the cytosol to enter the visual cycle. It also removes toxic retinoids from the disc lumen. Mutations in ABCA4 cause impaired vision or blindness. Despite decades of clinical, biochemical, and animal model studies, the molecular mechanism of ABCA4 is unknown. Here, we report the structures of human ABCA4 in two conformations. In the absence of ATP, ABCA4 adopts an outward-facing conformation, poised to recruit substrate. The presence of ATP induces large conformational changes that could lead to substrate release. These structures provide a molecular basis to understand many disease-causing mutations and a rational guide for new experiments to uncover how ABCA4 recruits, flips, and releases retinoids. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 157 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 12.3 KB 12.3 KB | Display Display | ![]() |
Images | ![]() | 91.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7lkpMC ![]() 7lkzC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data size: 1.9 TB Data #1: Unaligned and uncorrected multiframe movies of human ATP-free ABCA4 [micrographs - multiframe]) |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Structure of ATP-free human ABCA4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.03 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : ABCA4
Entire | Name: ABCA4 |
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Components |
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-Supramolecule #1: ABCA4
Supramolecule | Name: ABCA4 / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Retinal-specific phospholipid-transporting ATPase ABCA4
Macromolecule | Name: Retinal-specific phospholipid-transporting ATPase ABCA4 type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: P-type phospholipid transporter |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 256.202531 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MGFVRQIQLL LWKNWTLRKR QKIRFVVELV WPLSLFLVLI WLRNANPLYS HHECHFPNKA MPSAGMLPWL QGIFCNVNNP CFQSPTPGE SPGIVSNYNN SILARVYRDF QELLMNAPES QHLGRIWTEL HILSQFMDTL RTHPERIAGR GIRIRDILKD E ETLTLFLI ...String: MGFVRQIQLL LWKNWTLRKR QKIRFVVELV WPLSLFLVLI WLRNANPLYS HHECHFPNKA MPSAGMLPWL QGIFCNVNNP CFQSPTPGE SPGIVSNYNN SILARVYRDF QELLMNAPES QHLGRIWTEL HILSQFMDTL RTHPERIAGR GIRIRDILKD E ETLTLFLI KNIGLSDSVV YLLINSQVRP EQFAHGVPDL ALKDIACSEA LLERFIIFSQ RRGAKTVRYA LCSLSQGTLQ WI EDTLYAN VDFFKLFRVL PTLLDSRSQG INLRSWGGIL SDMSPRIQEF IHRPSMQDLL WVTRPLMQNG GPETFTKLMG ILS DLLCGY PEGGGSRVLS FNWYEDNNYK AFLGIDSTRK DPIYSYDRRT TSFCNALIQS LESNPLTKIA WRAAKPLLMG KILY TPDSP AARRILKNAN STFEELEHVR KLVKAWEEVG PQIWYFFDNS TQMNMIRDTL GNPTVKDFLN RQLGEEGITA EAILN FLYK GPRESQADDM ANFDWRDIFN ITDRTLRLVN QYLECLVLDK FESYNDETQL TQRALSLLEE NMFWAGVVFP DMYPWT SSL PPHVKYKIRM DIDVVEKTNK IKDRYWDSGP RADPVEDFRY IWGGFAYLQD MVEQGITRSQ VQAEAPVGIY LQQMPYP CF VDDSFMIILN RCFPIFMVLA WIYSVSMTVK SIVLEKELRL KETLKNQGVS NAVIWCTWFL DSFSIMSMSI FLLTIFIM H GRILHYSDPF ILFLFLLAFS TATIMLCFLL STFFSKASLA AACSGVIYFT LYLPHILCFA WQDRMTAELK KAVSLLSPV AFGFGTEYLV RFEEQGLGLQ WSNIGNSPTE GDEFSFLLSM QMMLLDAAVY GLLAWYLDQV FPGDYGTPLP WYFLLQESYW LGGEGCSTR EERALEKTEP LTEETEDPEH PEGIHDSFFE REHPGWVPGV CVKNLVKIFE PCGRPAVDRL NITFYENQIT A FLGHNGAG KTTTLSILTG LLPPTSGTVL VGGRDIETSL DAVRQSLGMC PQHNILFHHL TVAEHMLFYA QLKGKSQEEA QL EMEAMLE DTGLHHKRNE EAQDLSGGMQ RKLSVAIAFV GDAKVVILDE PTSGVDPYSR RSIWDLLLKY RSGRTIIMST HHM DEADLL GDRIAIIAQG RLYCSGTPLF LKNCFGTGLY LTLVRKMKNI QSQRKGSEGT CSCSSKGFST TCPAHVDDLT PEQV LDGDV NELMDVVLHH VPEAKLVECI GQELIFLLPN KNFKHRAYAS LFRELEETLA DLGLSSFGIS DTPLEEIFLK VTEDS DSGP LFAGGAQQKR ENVNPRHPCL GPREKAGQTP QDSNVCSPGA PAAHPEGQPP PEPECPGPQL NTGTQLVLQH VQALLV KRF QHTIRSHKDF LAQIVLPATF VFLALMLSIV IPPFGEYPAL TLHPWIYGQQ YTFFSMDEPG SEQFTVLADV LLNKPGF GN RCLKEGWLPE YPCGNSTPWK TPSVSPNITQ LFQKQKWTQV NPSPSCRCST REKLTMLPEC PEGAGGLPPP QRTQRSTE I LQDLTDRNIS DFLVKTYPAL IRSSLKSKFW VNEQRYGGIS IGGKLPVVPI TGEALVGFLS DLGRIMNVSG GPITREASK EIPDFLKHLE TEDNIKVWFN NKGWHALVSF LNVAHNAILR ASLPKDRSPE EYGITVISQP LNLTKEQLSE ITVLTTSVDA VVAICVIFS MSFVPASFVL YLIQERVNKS KHLQFISGVS PTTYWVTNFL WDIMNYSVSA GLVVGIFIGF QKKAYTSPEN L PALVALLL LYGWAVIPMM YPASFLFDVP STAYVALSCA NLFIGINSSA ITFILELFEN NRTLLRFNAV LRKLLIVFPH FC LGRGLID LALSQAVTDV YARFGEEHSA NPFHWDLIGK NLFAMVVEGV VYFLLTLLVQ RHFFLSQWIA EPTKEPIVDE DDD VAEERQ RIITGGNKTD ILRLHELTKI YPGTSSPAVD RLCVGVRPGE CFGLLGVNGA GKTTTFKMLT GDTTVTSGDA TVAG KSILT NISEVHQNMG YCPQFDAIDE LLTGREHLYL YARLRGVPAE EIEKVANWSI KSLGLTVYAD CLAGTYSGGN KRKLS TAIA LIGCPPLVLL DEPTTGMDPQ ARRMLWNVIV SIIREGRAVV LTSHSMEECE ALCTRLAIMV KGAFRCMGTI QHLKSK FGD GYIVTMKIKS PKDDLLPDLN PVEQFFQGNF PGSVQRERHY NMLQFQVSSS SLARIFQLLL SHKDSLLIEE YSVTQTT LD QVFVNFAKQQ TESHDLPLHP RAAGASRQAQ D |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 6 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Macromolecule #5: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 5 / Number of copies: 7 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-Macromolecule #6: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
Macromolecule | Name: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate type: ligand / ID: 6 / Number of copies: 7 / Formula: POV |
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Molecular weight | Theoretical: 760.076 Da |
Chemical component information | ![]() ChemComp-POV: |
-Macromolecule #7: Digitonin
Macromolecule | Name: Digitonin / type: ligand / ID: 7 / Number of copies: 1 / Formula: AJP |
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Molecular weight | Theoretical: 1.229312 KDa |
Chemical component information | ![]() ChemComp-AJP: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 5.5 mg/mL |
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Buffer | pH: 8 |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 1.51 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
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.27 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 320102 |
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Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: ANGULAR RECONSTITUTION |