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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-31000 | |||||||||
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Title | Cryo-EM structure of human ABCA4 in the apo state | |||||||||
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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 / phospholipid translocation / lipid transport / 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: 3.3 Å | |||||||||
![]() | Xie T / Zhang ZK / Gong X | |||||||||
![]() | ![]() Title: Structural basis of substrate recognition and translocation by human ABCA4. Authors: Tian Xie / Zike Zhang / Qi Fang / Bowen Du / Xin Gong / ![]() Abstract: Human ATP-binding cassette (ABC) subfamily A (ABCA) transporters mediate the transport of various lipid compounds across the membrane. Mutations in human ABCA transporters have been described to ...Human ATP-binding cassette (ABC) subfamily A (ABCA) transporters mediate the transport of various lipid compounds across the membrane. Mutations in human ABCA transporters have been described to cause severe hereditary disorders associated with impaired lipid transport. However, little is known about the mechanistic details of substrate recognition and translocation by ABCA transporters. Here, we present three cryo-EM structures of human ABCA4, a retina-specific ABCA transporter, in distinct functional states at resolutions of 3.3-3.4 Å. In the nucleotide-free state, the two transmembrane domains (TMDs) exhibit a lateral-opening conformation, allowing the lateral entry of substrate from the lipid bilayer. The N-retinylidene-phosphatidylethanolamine (NRPE), the physiological lipid substrate of ABCA4, is sandwiched between the two TMDs in the luminal leaflet and is further stabilized by an extended loop from extracellular domain 1. In the ATP-bound state, the two TMDs display a closed conformation, which precludes the substrate binding. Our study provides a molecular basis to understand the mechanism of ABCA4-mediated NRPE recognition and translocation, and suggests a common 'lateral access and extrusion' mechanism for ABCA-mediated lipid transport. | |||||||||
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 | ![]() | 78.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 11.4 KB 11.4 KB | Display Display | ![]() |
Images | ![]() | 37.9 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7e7iMC ![]() 7e7oC ![]() 7e7qC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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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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Voxel size | X=Y=Z: 1.08 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: complex / 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: 261.143547 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MADYKDDDDK SGPDEVDASG RMGFVRQIQL LLWKNWTLRK RQKIRFVVEL VWPLSLFLVL IWLRNANPLY SHHECHFPNK AMPSAGMLP WLQGIFCNVN NPCFQSPTPG ESPGIVSNYN NSILARVYRD FQELLMNAPE SQHLGRIWTE LHILSQFMDT L RTHPERIA ...String: MADYKDDDDK SGPDEVDASG RMGFVRQIQL LLWKNWTLRK RQKIRFVVEL VWPLSLFLVL IWLRNANPLY SHHECHFPNK AMPSAGMLP WLQGIFCNVN NPCFQSPTPG ESPGIVSNYN NSILARVYRD FQELLMNAPE SQHLGRIWTE LHILSQFMDT L RTHPERIA GRGIRIRDIL KDEETLTLFL IKNIGLSDSV VYLLINSQVR PEQFAHGVPD LALKDIACSE ALLERFIIFS QR RGAKTVR YALCSLSQGT LQWIEDTLYA NVDFFKLFRV LPTLLDSRSQ GINLRSWGGI LSDMSPRIQE FIHRPSMQDL LWV TRPLMQ NGGPETFTKL MGILSDLLCG YPEGGGSRVL SFNWYEDNNY KAFLGIDSTR KDPIYSYDRR TTSFCNALIQ SLES NPLTK IAWRAAKPLL MGKILYTPDS PAARRILKNA NSTFEELEHV RKLVKAWEEV GPQIWYFFDN STQMNMIRDT LGNPT VKDF LNRQLGEEGI TAEAILNFLY KGPRESQADD MANFDWRDIF NITDRTLRLV NQYLECLVLD KFESYNDETQ LTQRAL SLL EENMFWAGVV FPDMYPWTSS LPPHVKYKIR MDIDVVEKTN KIKDRYWDSG PRADPVEDFR YIWGGFAYLQ DMVEQGI TR SQVQAEAPVG IYLQQMPYPC FVDDSFMIIL NRCFPIFMVL AWIYSVSMTV KSIVLEKELR LKETLKNQGV SNAVIWCT W FLDSFSIMSM SIFLLTIFIM HGRILHYSDP FILFLFLLAF STATIMLCFL LSTFFSKASL AAACSGVIYF TLYLPHILC FAWQDRMTAE LKKAVSLLSP VAFGFGTEYL VRFEEQGLGL QWSNIGNSPT EGDEFSFLLS MQMMLLDAAV YGLLAWYLDQ VFPGDYGTP LPWYFLLQES YWLGGEGCST REERALEKTE PLTEETEDPE HPEGIHDSFF EREHPGWVPG VCVKNLVKIF E PCGRPAVD RLNITFYENQ ITAFLGHNGA GKTTTLSILT GLLPPTSGTV LVGGRDIETS LDAVRQSLGM CPQHNILFHH LT VAEHMLF YAQLKGKSQE EAQLEMEAML EDTGLHHKRN EEAQDLSGGM QRKLSVAIAF VGDAKVVILD EPTSGVDPYS RRS IWDLLL KYRSGRTIIM STHHMDEADL LGDRIAIIAQ GRLYCSGTPL FLKNCFGTGL YLTLVRKMKN IQSQRKGSEG TCSC SSKGF STTCPAHVDD LTPEQVLDGD VNELMDVVLH HVPEAKLVEC IGQELIFLLP NKNFKHRAYA SLFRELEETL ADLGL SSFG ISDTPLEEIF LKVTEDSDSG PLFAGGAQQK RENVNPRHPC LGPREKAGQT PQDSNVCSPG APAAHPEGQP PPEPEC PGP QLNTGTQLVL QHVQALLVKR FQHTIRSHKD FLAQIVLPAT FVFLALMLSI VIPPFGEYPA LTLHPWIYGQ QYTFFSM DE PGSEQFTVLA DVLLNKPGFG NRCLKEGWLP EYPCGNSTPW KTPSVSPNIT QLFQKQKWTQ VNPSPSCRCS TREKLTML P ECPEGAGGLP PPQRTQRSTE ILQDLTDRNI SDFLVKTYPA LIRSSLKSKF WVNEQRYGGI SIGGKLPVVP ITGEALVGF LSDLGRIMNV SGGPITREAS KEIPDFLKHL ETEDNIKVWF NNKGWHALVS FLNVAHNAIL RASLPKDRSP EEYGITVISQ PLNLTKEQL SEITVLTTSV DAVVAICVIF SMSFVPASFV LYLIQERVNK SKHLQFISGV SPTTYWVTNF LWDIMNYSVS A GLVVGIFI GFQKKAYTSP ENLPALVALL LLYGWAVIPM MYPASFLFDV PSTAYVALSC ANLFIGINSS AITFILELFE NN RTLLRFN AVLRKLLIVF PHFCLGRGLI DLALSQAVTD VYARFGEEHS ANPFHWDLIG KNLFAMVVEG VVYFLLTLLV QRH FFLSQW IAEPTKEPIV DEDDDVAEER QRIITGGNKT DILRLHELTK IYPGTSSPAV DRLCVGVRPG ECFGLLGVNG AGKT TTFKM LTGDTTVTSG DATVAGKSIL TNISEVHQNM GYCPQFDAID ELLTGREHLY LYARLRGVPA EEIEKVANWS IKSLG LTVY ADCLAGTYSG GNKRKLSTAI ALIGCPPLVL LDEPTTGMDP QARRMLWNVI VSIIREGRAV VLTSHSMEEC EALCTR LAI MVKGAFRCMG TIQHLKSKFG DGYIVTMKIK SPKDDLLPDL NPVEQFFQGN FPGSVQRERH YNMLQFQVSS SSLARIF QL LLSHKDSLLI EEYSVTQTTL DQVFVNFAKQ QTESHDLPLH PRAAGASRQA QDLEGSDEVD AVEGSHHHHH HHHHH |
-Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 3 / Number of copies: 7 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Macromolecule #4: 1,2-Distearoyl-sn-glycerophosphoethanolamine
Macromolecule | Name: 1,2-Distearoyl-sn-glycerophosphoethanolamine / type: ligand / ID: 4 / Number of copies: 2 / Formula: 3PE |
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Molecular weight | Theoretical: 748.065 Da |
Chemical component information | ![]() ChemComp-3PE: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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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: 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
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 205597 |
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Initial angle assignment | Type: NOT APPLICABLE |
Final angle assignment | Type: NOT APPLICABLE |