7auw
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Inhibitory complex of human meprin beta with mouse fetuin-B.== |
| - | <StructureSection load='7auw' size='340' side='right'caption='[[7auw]]' scene=''> | + | <StructureSection load='7auw' size='340' side='right'caption='[[7auw]], [[Resolution|resolution]] 2.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7auw]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AUW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AUW FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7auw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7auw OCA], [https://pdbe.org/7auw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7auw RCSB], [https://www.ebi.ac.uk/pdbsum/7auw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7auw ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7auw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7auw OCA], [https://pdbe.org/7auw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7auw RCSB], [https://www.ebi.ac.uk/pdbsum/7auw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7auw ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MEP1B_HUMAN MEP1B_HUMAN] Membrane metallopeptidase that sheds many membrane-bound proteins. Known substrates include: FGF19, VGFA, IL1B, IL18, procollagen I and III, E-cadherin, KLK7, gastrin, ADAM10, tenascin-C. The presence of several pro-inflammatory cytokine among substrates implicate MEP1B in inflammation. It is also involved in tissue remodeling due to its capability to degrade extracellular matrix components.<ref>PMID:21693781</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Meprin beta (Mbeta) is a multidomain type-I membrane metallopeptidase that sheds membrane-anchored substrates, releasing their soluble forms. Fetuin-B (FB) is its only known endogenous protein inhibitor. Herein, we analyzed the interaction between the ectodomain of Mbeta (MbetaDeltaC) and FB, which stabilizes the enzyme and inhibits it with subnanomolar affinity. The MbetaDeltaC:FB crystal structure reveals a approximately 250-kDa, approximately 160-A polyglycosylated heterotetrameric particle with a remarkable glycan structure. Two FB moieties insert like wedges through a "CPDCP trunk" and two hairpins into the respective peptidase catalytic domains, blocking the catalytic zinc ions through an "aspartate switch" mechanism. Uniquely, the active site clefts are obstructed from subsites S(4) to S(10)', but S(1) and S(1)' are spared, which prevents cleavage. Modeling of full-length Mbeta reveals an EGF-like domain between MbetaDeltaC and the transmembrane segment that likely serves as a hinge to transit between membrane-distal and membrane-proximal conformations for inhibition and catalysis, respectively. | ||
| + | |||
| + | The crystal structure of a 250-kDa heterotetrameric particle explains inhibition of sheddase meprin beta by endogenous fetuin-B.,Eckhard U, Korschgen H, von Wiegen N, Stocker W, Gomis-Ruth FX Proc Natl Acad Sci U S A. 2021 Apr 6;118(14):e2023839118. doi: , 10.1073/pnas.2023839118. PMID:33782129<ref>PMID:33782129</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7auw" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Mus musculus]] |
| + | [[Category: Eckhard U]] | ||
| + | [[Category: Gomis-Ruth FX]] | ||
Current revision
Inhibitory complex of human meprin beta with mouse fetuin-B.
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