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Yorodumi- EMDB-24922: Cryo-EM structure of a mammalian peptide transporter (PepT1/slc15... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-24922 | |||||||||||||||||||||
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Title | Cryo-EM structure of a mammalian peptide transporter (PepT1/slc15a1) in nanodisc | |||||||||||||||||||||
Map data | Cryo-EM map of horse PepT1 in nanodisc | |||||||||||||||||||||
Sample |
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Function / homology | Function and homology information proton-dependent oligopeptide secondary active transmembrane transporter activity / dipeptide import across plasma membrane / peptide:proton symporter activity / dipeptide transmembrane transporter activity / plasma membrane => GO:0005886 / brush border Similarity search - Function | |||||||||||||||||||||
Biological species | Equus caballus (horse) | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.7 Å | |||||||||||||||||||||
Authors | Shen J / Zhou M | |||||||||||||||||||||
Funding support | United States, 6 items
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Citation | Journal: Structure / Year: 2022 Title: Extracellular domain of PepT1 interacts with TM1 to facilitate substrate transport. Authors: Jiemin Shen / Miaohui Hu / Xiao Fan / Zhenning Ren / Corinne Portioli / Xiuwen Yan / Mingqiang Rong / Ming Zhou / Abstract: Mammalian peptide transporters, PepT1 and PepT2, mediate uptake of small peptides and are essential for their absorption. PepT also mediates absorption of many drugs and prodrugs to enhance their ...Mammalian peptide transporters, PepT1 and PepT2, mediate uptake of small peptides and are essential for their absorption. PepT also mediates absorption of many drugs and prodrugs to enhance their bioavailability. PepT has twelve transmembrane (TM) helices that fold into an N-terminal domain (NTD, TM1-6) and a C-terminal domain (CTD, TM7-12) and has a large extracellular domain (ECD) between TM9-10. It is well recognized that peptide transport requires movements of the NTD and CTD, but the role of the ECD in PepT1 remains unclear. Here we report the structure of horse PepT1 encircled in lipid nanodiscs and captured in the inward-open apo conformation. The structure shows that the ECD bridges the NTD and CTD by interacting with TM1. Deletion of ECD or mutations to the ECD-TM1 interface impairs the transport activity. These results demonstrate an important role of ECD in PepT1 and enhance our understanding of the transport mechanism in PepT1. | |||||||||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_24922.map.gz | 28.7 MB | EMDB map data format | |
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Header (meta data) | emd-24922-v30.xml emd-24922.xml | 11.4 KB 11.4 KB | Display Display | EMDB header |
Images | emd_24922.png | 99.6 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-24922 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-24922 | HTTPS FTP |
-Validation report
Summary document | emd_24922_validation.pdf.gz | 373.5 KB | Display | EMDB validaton report |
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Full document | emd_24922_full_validation.pdf.gz | 373.1 KB | Display | |
Data in XML | emd_24922_validation.xml.gz | 5.4 KB | Display | |
Data in CIF | emd_24922_validation.cif.gz | 6.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24922 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24922 | HTTPS FTP |
-Related structure data
Related structure data | 7s8uMC 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_24922.map.gz / Format: CCP4 / Size: 30.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | Cryo-EM map of horse PepT1 in nanodisc | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.114 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : PepT1 in MSP1D1 nanodisc
Entire | Name: PepT1 in MSP1D1 nanodisc |
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Components |
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-Supramolecule #1: PepT1 in MSP1D1 nanodisc
Supramolecule | Name: PepT1 in MSP1D1 nanodisc / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Equus caballus (horse) |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
-Macromolecule #1: Solute carrier family 15 member 1
Macromolecule | Name: Solute carrier family 15 member 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Equus caballus (horse) |
Molecular weight | Theoretical: 78.723992 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MGMSRSQSCF GYPLSIFFIV VNEFCERFSY YGMRALLILY FTLFIGWDDN LSTAIYHTFV ALCYLTPILG ALIADSWLGK FKTIVSLSI VYTIGQVVLA VSSINDLTDG NRDGTPDSLP VHVALSMIGL ALIAFGTGGI KPCVSAFGGD QFEEGQEKQR N RFFSIFYL ...String: MGMSRSQSCF GYPLSIFFIV VNEFCERFSY YGMRALLILY FTLFIGWDDN LSTAIYHTFV ALCYLTPILG ALIADSWLGK FKTIVSLSI VYTIGQVVLA VSSINDLTDG NRDGTPDSLP VHVALSMIGL ALIAFGTGGI KPCVSAFGGD QFEEGQEKQR N RFFSIFYL AINAGSLLST IITPILRVQQ CGIHSKQACY PLAFGVPAAL MAVSLIVFVI GSRMYKKFQP QGNIMAKVAK CI GFAITNR IRHRSNKFPK REHWLDWAKE KYDERLISQI KMVTRVMFLY IPLPMFWALF DQQGSRWTLQ ATTMNGQIGV IEI QPDQMQ TVNAILIVIM VPIMDAVVYP LIAKCGLNFT SLKKMTVGMF LASMAFVAAA IVQVEIDKTL PVFPNGHEVQ VKVL NIGNN SMNISFPGET MAVNQMSQTG DFMTFDVDKL SINISSTGSP VTPVTHNFEQ GHRHTILVWA PNHYRVIKDG LDRKP EKGQ NGIRFVNAFD KSFDVTMDGT VYVNVTSHSA SEYQFFPSGK KSFTINSTEI SQQCERNFTS PRLGFGSAYT YVMGRK ADG CPELSVFGDI PPNTVNMALQ IPQYFLLTCG EVVFSVTGLE FSYSQAPSNM KSVLQAGWLL TVAVGNIIVL IVAGAGQ FS KQWAEYILFA ALLLVVCVIF GIMAQFYTYV NPAEVEAKFD DDEKKKNPEK ENPYYTLDSV SQTRM |
-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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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: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.1 µm / Nominal defocus min: 1.9000000000000001 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 315767 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |