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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Structure of Inactive-EP | |||||||||
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Function / homology | ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Yang XL / Ding ZY / Huang HJ | |||||||||
Funding support | 1 items
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![]() | ![]() Title: Cryo-EM structures reveal the activation and substrate recognition mechanism of human enteropeptidase. Authors: Xiaoli Yang / Zhanyu Ding / Lisi Peng / Qiuyue Song / Deyu Zhang / Fang Cui / Chuanchao Xia / Keliang Li / Hua Yin / Shiyu Li / Zhaoshen Li / Haojie Huang / ![]() Abstract: Enteropeptidase (EP) initiates intestinal digestion by proteolytically processing trypsinogen, generating catalytically active trypsin. EP dysfunction causes a series of pancreatic diseases including ...Enteropeptidase (EP) initiates intestinal digestion by proteolytically processing trypsinogen, generating catalytically active trypsin. EP dysfunction causes a series of pancreatic diseases including acute necrotizing pancreatitis. However, the molecular mechanisms of EP activation and substrate recognition remain elusive, due to the lack of structural information on the EP heavy chain. Here, we report cryo-EM structures of human EP in inactive, active, and substrate-bound states at resolutions from 2.7 to 4.9 Å. The EP heavy chain was observed to clamp the light chain with CUB2 domain for substrate recognition. The EP light chain N-terminus induced a rearrangement of surface-loops from inactive to active conformations, resulting in activated EP. The heavy chain then served as a hinge for light-chain conformational changes to recruit and subsequently cleave substrate. Our study provides structural insights into rearrangements of EP surface-loops and heavy chain dynamics in the EP catalytic cycle, advancing our understanding of EP-associated pancreatitis. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 33 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 10.2 KB 10.2 KB | Display Display | ![]() |
Images | ![]() | 80 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7wqxMC ![]() 7wqwC ![]() 7wqzC ![]() 7wr7C ![]() 8h3sC ![]() 8h3uC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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: 1.046 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : inactive-EP
Entire | Name: inactive-EP |
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Components |
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-Supramolecule #1: inactive-EP
Supramolecule | Name: inactive-EP / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
-Macromolecule #1: Enteropeptidase
Macromolecule | Name: Enteropeptidase / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: ![]() |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 55.51843 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: ELPTDCGGPF ELWEPNTTFS STNFPNSYPN LAFCVWILNA QKGKNIQLHF QEFDLENIND VVEIRDGEEA DSLLLAVYTG PGPVKDVFS TTNRMTVLLI TNDVLARGGF KANFTTGYHL GIPEPCKADH FQCKNGECVP LVNLCDGHLH CEDGSDEADC V RFFNGTTN ...String: ELPTDCGGPF ELWEPNTTFS STNFPNSYPN LAFCVWILNA QKGKNIQLHF QEFDLENIND VVEIRDGEEA DSLLLAVYTG PGPVKDVFS TTNRMTVLLI TNDVLARGGF KANFTTGYHL GIPEPCKADH FQCKNGECVP LVNLCDGHLH CEDGSDEADC V RFFNGTTN NNGLVRFRIQ SIWHTACAEN WTTQISNDVC QLLGLGSGNS SKPIFPTDGG PFVKLNTAPD GHLILTPSQQ CL QDSLIRL QCNHKSCGKK LAAQDITPKI VGGSNAKEGA WPWVVGLYYG GRLLCGASLV SSDWLVSAAH CVYGRNLEPS KWT AILGLH MKSNLTSPQT VPRLIDEIVI NPHYNRRRKD NDIAMMHLEF KVNYTDYIQP ICLPEENQVF PPGRNCSIAG WGTV VYQGT TANILQEADV PLLSNERCQQ QMPEYNITEN MICAGYEEGG IDSCQGDSGG PLMCQENNRW FLAGVTSFGY KCALP NRPG VYARVSRFTE WIQSFLH |
-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: 9 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.6 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 52.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Initial angle assignment | Type: PROJECTION MATCHING |
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Final angle assignment | Type: ANGULAR RECONSTITUTION |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 511658 |