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Yorodumi- EMDB-13544: HsPepT2 bound to Ala-Phe in the inward facing partially occluded ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-13544 | |||||||||
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Title | HsPepT2 bound to Ala-Phe in the inward facing partially occluded conformation | |||||||||
Map data | post processed in Phenix. Used for refinement | |||||||||
Sample |
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Keywords | HsPepT2 / PepT2 / Peptide transporter / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information tripeptide import across plasma membrane / Proton/oligopeptide cotransporters / peptidoglycan transport / dipeptide transport / tripeptide transmembrane transporter activity / dipeptide import across plasma membrane / antibacterial innate immune response / peptide:proton symporter activity / dipeptide transmembrane transporter activity / regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway ...tripeptide import across plasma membrane / Proton/oligopeptide cotransporters / peptidoglycan transport / dipeptide transport / tripeptide transmembrane transporter activity / dipeptide import across plasma membrane / antibacterial innate immune response / peptide:proton symporter activity / dipeptide transmembrane transporter activity / regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / xenobiotic detoxification by transmembrane export across the plasma membrane / peptide transport / xenobiotic transport / renal absorption / transport across blood-brain barrier / monoatomic ion transport / phagocytic vesicle membrane / protein transport / apical plasma membrane / extracellular exosome / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
Authors | Killer M / Wald J | |||||||||
Funding support | 1 items
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Citation | Journal: Sci Adv / Year: 2021 Title: Structural snapshots of human PepT1 and PepT2 reveal mechanistic insights into substrate and drug transport across epithelial membranes. Authors: Maxime Killer / Jiri Wald / Joanna Pieprzyk / Thomas C Marlovits / Christian Löw / Abstract: The uptake of peptides in mammals plays a crucial role in nutrition and inflammatory diseases. This process is mediated by promiscuous transporters of the solute carrier family 15, which form part of ...The uptake of peptides in mammals plays a crucial role in nutrition and inflammatory diseases. This process is mediated by promiscuous transporters of the solute carrier family 15, which form part of the major facilitator superfamily. Besides the uptake of short peptides, peptide transporter 1 (PepT1) is a highly abundant drug transporter in the intestine and represents a major route for oral drug delivery. PepT2 also allows renal drug reabsorption from ultrafiltration and brain-to-blood efflux of neurotoxic compounds. Here, we present cryogenic electron microscopy (cryo-EM) structures of human PepT1 and PepT2 captured in four different states throughout the transport cycle. The structures reveal the architecture of human peptide transporters and provide mechanistic insights into substrate recognition and conformational transitions during transport. This may support future drug design efforts to increase the bioavailability of different drugs in the human body. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_13544.map.gz | 57.5 MB | EMDB map data format | |
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Header (meta data) | emd-13544-v30.xml emd-13544.xml | 17.1 KB 17.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_13544_fsc.xml | 8.9 KB | Display | FSC data file |
Images | emd_13544.png | 71.3 KB | ||
Masks | emd_13544_msk_1.map | 64 MB | Mask map | |
Filedesc metadata | emd-13544.cif.gz | 5.7 KB | ||
Others | emd_13544_additional_1.map.gz emd_13544_half_map_1.map.gz emd_13544_half_map_2.map.gz | 56.5 MB 59.5 MB 59.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-13544 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-13544 | HTTPS FTP |
-Validation report
Summary document | emd_13544_validation.pdf.gz | 788.3 KB | Display | EMDB validaton report |
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Full document | emd_13544_full_validation.pdf.gz | 787.8 KB | Display | |
Data in XML | emd_13544_validation.xml.gz | 16.4 KB | Display | |
Data in CIF | emd_13544_validation.cif.gz | 21 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-13544 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-13544 | HTTPS FTP |
-Related structure data
Related structure data | 7pmyMC 7pmwC 7pmxC 7pn1C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_13544.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | post processed in Phenix. Used for refinement | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.85 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_13544_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: #1
File | emd_13544_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_13544_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_13544_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Human PepT2
Entire | Name: Human PepT2 |
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Components |
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-Supramolecule #1: Human PepT2
Supramolecule | Name: Human PepT2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #2: ALA-PHE
Supramolecule | Name: ALA-PHE / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Solute carrier family 15 member 2
Macromolecule | Name: Solute carrier family 15 member 2 / type: protein_or_peptide / ID: 1 / Details: HsPepT2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 81.861125 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MNPFQKNESK ETLFSPVSIE EVPPRPPSPP KKPSPTICGS NYPLSIAFIV VNEFCERFSY YGMKAVLILY FLYFLHWNED TSTSIYHAF SSLCYFTPIL GAAIADSWLG KFKTIIYLSL VYVLGHVIKS LGALPILGGQ VVHTVLSLIG LSLIALGTGG I KPCVAAFG ...String: MNPFQKNESK ETLFSPVSIE EVPPRPPSPP KKPSPTICGS NYPLSIAFIV VNEFCERFSY YGMKAVLILY FLYFLHWNED TSTSIYHAF SSLCYFTPIL GAAIADSWLG KFKTIIYLSL VYVLGHVIKS LGALPILGGQ VVHTVLSLIG LSLIALGTGG I KPCVAAFG GDQFEEKHAE ERTRYFSVFY LSINAGSLIS TFITPMLRGD VQCFGEDCYA LAFGVPGLLM VIALVVFAMG SK IYNKPPP EGNIVAQVFK CIWFAISNRF KNRSGDIPKR QHWLDWAAEK YPKQLIMDVK ALTRVLFLYI PLPMFWALLD QQG SRWTLQ AIRMNRNLGF FVLQPDQMQV LNPLLVLIFI PLFDFVIYRL VSKCGINFSS LRKMAVGMIL ACLAFAVAAA VEIK INEMA PAQPGPQEVF LQVLNLADDE VKVTVVGNEN NSLLIESIKS FQKTPHYSKL HLKTKSQDFH FHLKYHNLSL YTEHS VQEK NWYSLVIRED GNSISSMMVK DTESRTTNGM TTVRFVNTLH KDVNISLSTD TSLNVGEDYG VSAYRTVQRG EYPAVH CRT EDKNFSLNLG LLDFGAAYLF VITNNTNQGL QAWKIEDIPA NKMSIAWQLP QYALVTAGEV MFSVTGLEFS YSQAPSS MK SVLQAAWLLT IAVGNIIVLV VAQFSGLVQW AEFILFSCLL LVICLIFSIM GYYYVPVKTE DMRGPADKHI PHIQGNMI K LETKKTKL UniProtKB: Solute carrier family 15 member 2 |
-Macromolecule #2: ALA-PHE
Macromolecule | Name: ALA-PHE / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 236.267 Da |
Sequence | String: AF |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: PROPANE / Chamber humidity: 100 % / Chamber temperature: 278 K / Instrument: FEI VITROBOT MARK IV |
-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: 81.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |