+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-13580 | |||||||||
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Title | MUC2 Tubules of D1D2D3 domains | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information WxxW domain / Mucin-2 protein WxxW repeating region / : / C8 domain / Uncharacterised domain, cysteine-rich / C8 / von Willebrand factor, type D domain / von Willebrand factor type D domain / VWFD domain profile. / von Willebrand factor (vWF) type D domain ...WxxW domain / Mucin-2 protein WxxW repeating region / : / C8 domain / Uncharacterised domain, cysteine-rich / C8 / von Willebrand factor, type D domain / von Willebrand factor type D domain / VWFD domain profile. / von Willebrand factor (vWF) type D domain / C-terminal cystine knot signature. / von Willebrand factor (vWF) type C domain / Trypsin Inhibitor-like, cysteine rich domain / Serine protease inhibitor-like superfamily / Trypsin Inhibitor like cysteine rich domain / C-terminal cystine knot domain profile. / Cystine knot, C-terminal / C-terminal cystine knot-like domain (CTCK) / VWFC domain signature. / VWFC domain profile. / von Willebrand factor (vWF) type C domain / VWFC domain Similarity search - Domain/homology | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Javitt G / Fass D | |||||||||
Funding support | 1 items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2022 Title: Helical self-assembly of a mucin segment suggests an evolutionary origin for von Willebrand factor tubules. Authors: Gabriel Javitt / Deborah Fass / Abstract: The glycoprotein von Willebrand factor (VWF) contributes to hemostasis by stanching injuries in blood vessel walls. A distinctive feature of VWF is its assembly into long, helical tubules in ...The glycoprotein von Willebrand factor (VWF) contributes to hemostasis by stanching injuries in blood vessel walls. A distinctive feature of VWF is its assembly into long, helical tubules in endothelial cells prior to secretion. When VWF is released into the bloodstream, these tubules unfurl to release linear polymers that bind subendothelial collagen at wound sites, recruit platelets, and initiate the clotting cascade. VWF evolved from gel-forming mucins, the polymeric glycoproteins that coat and protect exposed epithelia. Despite the divergent function of VWF in blood vessel repair, sequence conservation and shared domain organization imply that VWF retained key aspects of the mucin bioassembly mechanism. Here, we show using cryo-electron microscopy that the ability to form tubules, a property hitherto thought to have arisen as a VWF adaptation to the vasculature, is a feature of the amino-terminal region of mucin. This segment of the human intestinal gel-forming mucin (MUC2) was found to self-assemble into tubules with a striking resemblance to those of VWF itself. To facilitate a comparison, we determined the residue-resolution structure of tubules formed by the homologous segment of VWF. The structures of the MUC2 and VWF tubules revealed the flexible joints and the intermolecular interactions required for tubule formation. Steric constraints in full-length MUC2 suggest that linear filaments, a previously observed supramolecular assembly form, are more likely than tubules to be the physiological mucin storage intermediate. Nevertheless, MUC2 tubules indicate a possible evolutionary origin for VWF tubules and elucidate design principles present in mucins and VWF. | |||||||||
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_13580.map.gz | 122 MB | EMDB map data format | |
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Header (meta data) | emd-13580-v30.xml emd-13580.xml | 11.5 KB 11.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_13580_fsc.xml | 13.9 KB | Display | FSC data file |
Images | emd_13580.png | 143.5 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-13580 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-13580 | HTTPS FTP |
-Validation report
Summary document | emd_13580_validation.pdf.gz | 443.4 KB | Display | EMDB validaton report |
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Full document | emd_13580_full_validation.pdf.gz | 442.9 KB | Display | |
Data in XML | emd_13580_validation.xml.gz | 13.8 KB | Display | |
Data in CIF | emd_13580_validation.cif.gz | 18.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-13580 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-13580 | HTTPS FTP |
-Related structure data
Related structure data | 7pp6MC 7pmvC 7pnfC 7povC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_13580.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.2885 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : MUC2 local refinement of 2 beads from D1D2D3 domain tubules
Entire | Name: MUC2 local refinement of 2 beads from D1D2D3 domain tubules |
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Components |
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-Supramolecule #1: MUC2 local refinement of 2 beads from D1D2D3 domain tubules
Supramolecule | Name: MUC2 local refinement of 2 beads from D1D2D3 domain tubules 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) / Recombinant strain: HEK 293F / Recombinant plasmid: pCDNA3.1 |
-Macromolecule #1: Mucin-2
Macromolecule | Name: Mucin-2 / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 137.642609 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: SELQTEGRTR NHGHNVCSTW GNFHYKTFDG DVFRFPGLCD YNFASDCRGS YKEFAVHLKR GPGQAEAPAG VESILLTIKD DTIYLTRHL AVLNGAVVST PHYSPGLLIE KSDAYTKVYS RAGLTLMWNR EDALMLELDT KFRNHTCGLC GDYNGLQSYS E FLSDGVLF ...String: SELQTEGRTR NHGHNVCSTW GNFHYKTFDG DVFRFPGLCD YNFASDCRGS YKEFAVHLKR GPGQAEAPAG VESILLTIKD DTIYLTRHL AVLNGAVVST PHYSPGLLIE KSDAYTKVYS RAGLTLMWNR EDALMLELDT KFRNHTCGLC GDYNGLQSYS E FLSDGVLF SPLEFGNMQK INQPDVVCED PEEEVAPASC SEHRAECERL LTAEAFADCQ DLVPLEPYLR ACQQDRCRCP GG DTCVCST VAEFSRQCSH AGGRPGNWRT ATLCPKTCPG NLVYLESGSP CMDTCSHLEV SSLCEEHRMD GCFCPEGTVY DDI GDSGCV PVSQCHCRLH GHLYTPGQEI TNDCEQCVCN AGRWVCKDLP CPGTCALEGG SHITTFDGKT YTFHGDCYYV LAKG DHNDS YALLGELAPC GSTDKQTCLK TVVLLADKKK NVVVFKSDGS VLLNELQVNL PHVTASFSVF RPSSYHIMVS MAIGV RLQV QLAPVMQLFV TLDQASQGQV QGLCGNFNGL EGDDFKTASG LVEATGAGFA NTWKAQSSCH DKLDWLDDPC SLNIES ANY AEHWCSLLKK TETPFGRCHS AVDPAEYYKR CKYDTCNCQN NEDCLCAALS SYARACTAKG VMLWGWREHV CNKDVGS CP NSQVFLYNLT TCQQTCRSLS EADSHCLEGF APVDGCGCPD HTFLDEKGRC VPLAKCSCYH RGLYLEAGDV VVRQEERC V CRDGRLHCRQ IRLIGQSCTA PKIHMDCSNL TALATSKPRA LSCQTLAAGY YHTECVSGCV CPDGLMDDGR GGCVVEKEC PCVHNNDLYS SGAKIKVDCN TCTCKRGRWV CTQAVCHGTC SIYGSGHYIT FDGKYYDFDG HCSYVAVQDY CGQNSSLGSF SIITENVPC GTTGVTCSKA IKIFMGRTEL KLEDKHRVVI QRDEGHHVAY TTREVGQYLV VESSTGIIVI WDKRTTVFIK L APSYKGTV CGLCGNFDHR SNNDFTTRDH MVVSSELDFG NSWKEAPTCP DVSTNPEPCS LNPHRRSWAE KQCSILKSSV FS ICHSKVD PKPFYEACVH DSCSCDTGGD CECFCSAVAS YAQECTKEGA CVFWRTPDLC PIFCDYYNPP HECEWHYEPC GNR SFETCR TINGIHSNIS VSYLEGCYPR CPKDRPIYEE DLKKCVTADK CGCYVEDTHY PPGASVPTEE TCKSCVCTNS SQVV CRPEE GKILNQTQDG AFCYWEICGP NGTVEKHFNI CSITHHHHHH |
-Macromolecule #3: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 3 / Number of copies: 12 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 8 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #5: water
Macromolecule | Name: water / type: ligand / ID: 5 / Number of copies: 92 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | helical array |
-Sample preparation
Buffer | pH: 5.4 |
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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 K3 BIOQUANTUM (6k x 4k) / Average electron dose: 48.0 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 |