7ued: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7ued]] is a 3 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=7UED OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UED FirstGlance]. <br> | <table><tr><td colspan='2'>[[7ued]] is a 3 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=7UED OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UED FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 3Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7ued FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ued OCA], [https://pdbe.org/7ued PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ued RCSB], [https://www.ebi.ac.uk/pdbsum/7ued PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ued ProSAT]</span></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=7ued FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ued OCA], [https://pdbe.org/7ued PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ued RCSB], [https://www.ebi.ac.uk/pdbsum/7ued PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ued ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/MSLN_HUMAN MSLN_HUMAN] Membrane-anchored forms may play a role in cellular adhesion.<ref>PMID:8288629</ref> <ref>PMID:14676194</ref> Megakaryocyte-potentiating factor (MPF) potentiates megakaryocyte colony formation in vitro.<ref>PMID:8288629</ref> <ref>PMID:14676194</ref> | [https://www.uniprot.org/uniprot/MSLN_HUMAN MSLN_HUMAN] Membrane-anchored forms may play a role in cellular adhesion.<ref>PMID:8288629</ref> <ref>PMID:14676194</ref> Megakaryocyte-potentiating factor (MPF) potentiates megakaryocyte colony formation in vitro.<ref>PMID:8288629</ref> <ref>PMID:14676194</ref> | ||
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== Publication Abstract from PubMed == | |||
The tumor-associated antigen mesothelin is expressed at high levels on the cell surface of many human cancers, while its expression in normal tissues is limited. The binding of mesothelin to the tumor-associated cancer antigen 125 (CA-125) can lead to heterotypic cell adhesion and tumor metastasis within the pleural and peritoneal cavities. Immunotherapeutic strategies targeting mesothelin are being intensively investigated. Here, we report the crystal structures of mesothelin that reveal a compact, right-handed solenoid consisting of 24 short helices and connecting loops. These helices form a nine-layered spiral coil that resembles ARM/HEAT family proteins. Glycan attachments have been identified in the structure for all three predicted N-glycosylation sites and confirmed with samples from cell culture and patient ascites. The structures of full-length mesothelin and its complex with the Fab of MORAb-009 reveal the interaction of the antibody with the complete epitope, which has not been reported previously. The N-terminal half of mesothelin is conformationally rigid, suitable for eliciting specific antibodies, whereas its C-terminal portion is more flexible. The structure of the C-terminal shedding-resistant fragment of mesothelin complexed with a mAb 15B6 displays an extended linear epitope and helps explain the protection afforded by the antibody for the shedding sites. SIGNIFICANCE: The structures of full-length mesothelin and its complexes with antibodies reported here are the first to be determined experimentally, providing atomic models for structural organization of this protein and its interactions with antibodies. It offers insights into the function of mesothelin and guidance for further development of therapeutic antibodies. | |||
Structures of Cancer Antigen Mesothelin and Its Complexes with Therapeutic Antibodies.,Zhan J, Lin D, Watson N, Esser L, Tang WK, Zhang A, Liu X, Hassan R, Gleinich A, Shajahan A, Azadi P, Pastan I, Xia D Cancer Res Commun. 2023 Feb 1;3(2):175-191. doi: 10.1158/2767-9764.CRC-22-0306. , eCollection 2023 Feb. PMID:36968141<ref>PMID:36968141</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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== References == | == References == | ||
<references/> | <references/> | ||