+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-32233 | |||||||||
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Title | Cryo-EM structure of nucleotide-free ABCA3 | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information lamellar body membrane / Defective ABCA3 causes SMDP3 / Defective ABCA3 causes SMDP3 / alveolar lamellar body membrane / positive regulation of protein homooligomerization / regulation of phosphatidylcholine metabolic process / phosphatidylcholine transfer activity / lamellar body / positive regulation of phospholipid transport / xenobiotic export from cell ...lamellar body membrane / Defective ABCA3 causes SMDP3 / Defective ABCA3 causes SMDP3 / alveolar lamellar body membrane / positive regulation of protein homooligomerization / regulation of phosphatidylcholine metabolic process / phosphatidylcholine transfer activity / lamellar body / positive regulation of phospholipid transport / xenobiotic export from cell / alveolar lamellar body / organelle assembly / phosphatidylcholine flippase activity / positive regulation of phospholipid efflux / lipid transporter activity / ABC transporters in lipid homeostasis / phosphatidylglycerol metabolic process / regulation of lipid biosynthetic process / phosphatidylcholine metabolic process / xenobiotic transmembrane transport / phospholipid homeostasis / Surfactant metabolism / multivesicular body membrane / phospholipid transport / ABC-type xenobiotic transporter / protein metabolic process / surfactant homeostasis / P-type phospholipid transporter / ABC-type xenobiotic transporter activity / xenobiotic transport / lipid transport / positive regulation of cholesterol efflux / ATPase-coupled transmembrane transporter activity / response to glucocorticoid / lung development / cytoplasmic vesicle membrane / late endosome / membrane => GO:0016020 / response to xenobiotic stimulus / lysosomal membrane / intracellular membrane-bounded organelle / ATP hydrolysis activity / extracellular space / ATP binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Xie T / Zhang ZK / Yue J / Gong X | |||||||||
Funding support | 1 items
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Citation | Journal: Sci Adv / Year: 2022 Title: Cryo-EM structures of the human surfactant lipid transporter ABCA3. Authors: Tian Xie / Zike Zhang / Jian Yue / Qi Fang / Xin Gong / Abstract: The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter ABCA3 plays a critical role in pulmonary surfactant biogenesis. Mutations in human ABCA3 have been recognized as the most ...The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter ABCA3 plays a critical role in pulmonary surfactant biogenesis. Mutations in human ABCA3 have been recognized as the most frequent causes of inherited surfactant dysfunction disorders. Despite two decades of research, in vitro biochemical and structural studies of ABCA3 are still lacking. Here, we report the cryo-EM structures of human ABCA3 in two distinct conformations, both at resolution of 3.3 Å. In the absence of ATP, ABCA3 adopts a "lateral-opening" conformation with the lateral surfaces of transmembrane domains (TMDs) exposed to the membrane and features two positively charged cavities within the TMDs as potential substrate binding sites. ATP binding induces pronounced conformational changes, resulting in the collapse of the potential substrate binding cavities. Our results help to rationalize the disease-causing mutations in human ABCA3 and suggest a conserved "lateral access and extrusion" mechanism for both lipid export and import mediated by ABCA transporters. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_32233.map.gz | 49.4 MB | EMDB map data format | |
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Header (meta data) | emd-32233-v30.xml emd-32233.xml | 11.7 KB 11.7 KB | Display Display | EMDB header |
Images | emd_32233.png | 31 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-32233 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32233 | HTTPS FTP |
-Related structure data
Related structure data | 7w01MC 7w02C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_32233.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : ABCA3
Entire | Name: ABCA3 |
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Components |
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-Supramolecule #1: ABCA3
Supramolecule | Name: ABCA3 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: Phospholipid-transporting ATPase ABCA3
Macromolecule | Name: Phospholipid-transporting ATPase ABCA3 / 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: Homo sapiens (human) |
Molecular weight | Theoretical: 196.513656 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MADYKDDDDK SGPDEVDASG RMAVLRQLAL LLWKNYTLQK RKVLVTVLEL FLPLLFSGIL IWLRLKIQSE NVPNATIYPG QSIQELPLF FTFPPPGDTW ELAYIPSHSD AAKTVTETVR RALVINMRVR GFPSEKDFED YIRYDNCSSS VLAAVVFEHP F NHSKEPLP ...String: MADYKDDDDK SGPDEVDASG RMAVLRQLAL LLWKNYTLQK RKVLVTVLEL FLPLLFSGIL IWLRLKIQSE NVPNATIYPG QSIQELPLF FTFPPPGDTW ELAYIPSHSD AAKTVTETVR RALVINMRVR GFPSEKDFED YIRYDNCSSS VLAAVVFEHP F NHSKEPLP LAVKYHLRFS YTRRNYMWTQ TGSFFLKETE GWHTTSLFPL FPNPGPREPT SPDGGEPGYI REGFLAVQHA VD RAIMEYH ADAATRQLFQ RLTVTIKRFP YPPFIADPFL VAIQYQLPLL LLLSFTYTAL TIARAVVQEK ERRLKEYMRM MGL SSWLHW SAWFLLFFLF LLIAASFMTL LFCVKVKPNV AVLSRSDPSL VLAFLLCFAI STISFSFMVS TFFSKANMAA AFGG FLYFF TYIPYFFVAP RYNWMTLSQK LCSCLLSNVA MAMGAQLIGK FEAKGMGIQW RDLLSPVNVD DDFCFGQVLG MLLLD SVLY GLVTWYMEAV FPGQFGVPQP WYFFIMPSYW CGKPRAVAGK EEEDSDPEKA LRNEYFEAEP EDLVAGIKIK HLSKVF RVG NKDRAAVRDL NLNLYEGQIT VLLGHNGAGK TTTLSMLTGL FPPTSGRAYI SGYEISQDMV QIRKSLGLCP QHDILFD NL TVAEHLYFYA QLKGLSRQKC PEEVKQMLHI IGLEDKWNSR SRFLSGGMRR KLSIGIALIA GSKVLILDEP TSGMDAIS R RAIWDLLQRQ KSDRTIVLTT HFMDEADLLG DRIAIMAKGE LQCCGSSLFL KQKYGAGYHM TLVKEPHCNP EDISQLVHH HVPNATLESS AGAELSFILP RESTHRFEGL FAKLEKKQKE LGIASFGASI TTMEEVFLRV GKLVDSSMDI QAIQLPALQY QHERRASDW AVDSNLCGAM DPSDGIGALI EEERTAVKLN TGLALHCQQF WAMFLKKAAY SWREWKMVAA QVLVPLTCVT L ALLAINYS SELFDDPMLR LTLGEYGRTV VPFSVPGTSQ LGQQLSEHLK DALQAEGQEP REVLGDLEEF LIFRASVEGG GF NERCLVA ASFRDVGERT VVNALFNNQA YHSPATALAV VDNLLFKLLC GPHASIVVSN FPQPRSALQA AKDQFNEGRK GFD IALNLL FAMAFLASTF SILAVSERAV QAKHVQFVSG VHVASFWLSA LLWDLISFLI PSLLLLVVFK AFDVRAFTRD GHMA DTLLL LLLYGWAIIP LMYLMNFFFL GAATAYTRLT IFNILSGIAT FLMVTIMRIP AVKLEELSKT LDHVFLVLPN HCLGM AVSS FYENYETRRY CTSSEVAAHY CKKYNIQYQE NFYAWSAPGV GRFVASMAAS GCAYLILLFL IETNLLQRLR GILCAL RRR RTLTELYTRM PVLPEDQDVA DERTRILAPS PDSLLHTPLI IKELSKVYEQ RVPLLAVDRL SLAVQKGECF GLLGFNG AG KTTTFKMLTG EESLTSGDAF VGGHRISSDV GKVRQRIGYC PQFDALLDHM TGREMLVMYA RLRGIPERHI GACVENTL R GLLLEPHANK LVRTYSGGNK RKLSTGIALI GEPAVIFLDE PSTGMDPVAR RLLWDTVARA RESGKAIIIT SHSMEECEA LCTRLAIMVQ GQFKCLGSPQ HLKSKFGSGY SLRAKVQSEG QQEALEEFKA FVDLTFPGSV LEDEHQGMVH YHLPGRDLSW AKVFGILEK AKEKYGVDDY SVSQISLEQV FLSFAHLQPP TAEEGRLEGS DEVDAVEGSH HHHHHHHHH |
-Macromolecule #2: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 2 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #3: 1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE
Macromolecule | Name: 1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / type: ligand / ID: 3 / Number of copies: 2 / Formula: PX4 |
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Molecular weight | Theoretical: 678.94 Da |
Chemical component information | ChemComp-PX4: |
-Macromolecule #4: (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: 4 / Number of copies: 3 / Formula: POV |
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Molecular weight | Theoretical: 760.076 Da |
Chemical component information | ChemComp-POV: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Initial angle assignment | Type: NOT APPLICABLE |
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Final angle assignment | Type: NOT APPLICABLE |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 111435 |