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| | <StructureSection load='4f3f' size='340' side='right'caption='[[4f3f]], [[Resolution|resolution]] 2.65Å' scene=''> | | <StructureSection load='4f3f' size='340' side='right'caption='[[4f3f]], [[Resolution|resolution]] 2.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4f3f]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4F3F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F3F FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4f3f]] 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=4F3F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F3F FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4f33|4f33]]</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=4f3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f3f OCA], [https://pdbe.org/4f3f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f3f RCSB], [https://www.ebi.ac.uk/pdbsum/4f3f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f3f ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MSLN, MPF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4f3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f3f OCA], [http://pdbe.org/4f3f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4f3f RCSB], [http://www.ebi.ac.uk/pdbsum/4f3f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4f3f ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/MSLN_HUMAN MSLN_HUMAN]] Antibodies against MSLN are detected in patients with mesothelioma and ovarian cancer. | + | [https://www.uniprot.org/uniprot/MSLN_HUMAN MSLN_HUMAN] Antibodies against MSLN are detected in patients with mesothelioma and ovarian cancer. |
| | == Function == | | == Function == |
| - | [[http://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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 26: |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Esser, L]] | + | [[Category: Esser L]] |
| - | [[Category: Ma, J]] | + | [[Category: Ma J]] |
| - | [[Category: Pastan, I]] | + | [[Category: Pastan I]] |
| - | [[Category: Tang, W K]] | + | [[Category: Tang WK]] |
| - | [[Category: Xia, D]] | + | [[Category: Xia D]] |
| - | [[Category: Antibody fab]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Mesothelin]]
| + | |
| - | [[Category: Recognize mesothelin]]
| + | |
| Structural highlights
Disease
MSLN_HUMAN Antibodies against MSLN are detected in patients with mesothelioma and ovarian cancer.
Function
MSLN_HUMAN Membrane-anchored forms may play a role in cellular adhesion.[1] [2] Megakaryocyte-potentiating factor (MPF) potentiates megakaryocyte colony formation in vitro.[3] [4]
Publication Abstract from PubMed
Mesothelin is a tumor differentiation antigen that is highly expressed in many epithelial cancers, with limited expression in normal human tissues. Binding of mesothelin on normal mesothelial cells lining the pleura or peritoneum to the tumor-associated cancer antigen 125 (CA-125) can lead to heterotypic cell adhesion and tumor metastasis within the pleural and peritoneal cavities. This binding can be prevented by MORAb-009, a humanized monoclonal antibody against mesothelin currently under clinical trials. We show here that MORAb-009 recognizes a non-linear epitope that is contained in the first 64-residue fragment of the mesothelin. We further demonstrate that the recognition is independent of glycosylation state of the protein but sensitive to the loss of a disulfide bond linking residues Cys-7 and Cys-31. The crystal structure of the complex between the mesothelin N-terminal fragment and Fab of MORAb-009 at 2.6 A resolution reveals an epitope encompassing multiple secondary structural elements of the mesothelin, including residues from helix alpha1, the loops linking helices alpha1 and alpha2, and between helices alpha4 and alpha5. The mesothelin fragment has a compact, right-handed superhelix structure consisting of five short helices and connecting loops. A residue essential for complex formation has been identified as Phe-22, which projects its side chain into a hydrophobic niche formed on the antibody recognition surface upon antigen-antibody contact. The overlapping binding footprints of both the monoclonal antibody and the cancer antigen CA-125 explains the therapeutic effect and provides a basis for further antibody improvement.
Recognition of mesothelin by the therapeutic antibody MORAb-009: structural and mechanistic insights.,Ma J, Tang WK, Esser L, Pastan I, Xia D J Biol Chem. 2012 Sep 28;287(40):33123-31. Epub 2012 Jul 11. PMID:22787150[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yamaguchi N, Hattori K, Oh-eda M, Kojima T, Imai N, Ochi N. A novel cytokine exhibiting megakaryocyte potentiating activity from a human pancreatic tumor cell line HPC-Y5. J Biol Chem. 1994 Jan 14;269(2):805-8. PMID:8288629
- ↑ Rump A, Morikawa Y, Tanaka M, Minami S, Umesaki N, Takeuchi M, Miyajima A. Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion. J Biol Chem. 2004 Mar 5;279(10):9190-8. Epub 2003 Dec 15. PMID:14676194 doi:http://dx.doi.org/10.1074/jbc.M312372200
- ↑ Yamaguchi N, Hattori K, Oh-eda M, Kojima T, Imai N, Ochi N. A novel cytokine exhibiting megakaryocyte potentiating activity from a human pancreatic tumor cell line HPC-Y5. J Biol Chem. 1994 Jan 14;269(2):805-8. PMID:8288629
- ↑ Rump A, Morikawa Y, Tanaka M, Minami S, Umesaki N, Takeuchi M, Miyajima A. Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion. J Biol Chem. 2004 Mar 5;279(10):9190-8. Epub 2003 Dec 15. PMID:14676194 doi:http://dx.doi.org/10.1074/jbc.M312372200
- ↑ Ma J, Tang WK, Esser L, Pastan I, Xia D. Recognition of mesothelin by the therapeutic antibody MORAb-009: structural and mechanistic insights. J Biol Chem. 2012 Sep 28;287(40):33123-31. Epub 2012 Jul 11. PMID:22787150 doi:http://dx.doi.org/10.1074/jbc.M112.381756
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