7sa9
From Proteopedia
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==Human MUC16 SEA5 Domain== | ==Human MUC16 SEA5 Domain== | ||
| - | <StructureSection load='7sa9' size='340' side='right'caption='[[7sa9]]' scene=''> | + | <StructureSection load='7sa9' size='340' side='right'caption='[[7sa9]], [[Resolution|resolution]] 1.69Å' 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=7SA9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SA9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7sa9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SA9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SA9 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=7sa9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sa9 OCA], [https://pdbe.org/7sa9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sa9 RCSB], [https://www.ebi.ac.uk/pdbsum/7sa9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sa9 ProSAT]</span></td></tr> | </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=7sa9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sa9 OCA], [https://pdbe.org/7sa9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sa9 RCSB], [https://www.ebi.ac.uk/pdbsum/7sa9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sa9 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/MUC16_HUMAN MUC16_HUMAN]] Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | MUC16 is a membrane bound glycoprotein involved in the progression and metastasis of pancreatic and ovarian cancer. The protein is shed into the serum and the resulting cancer antigen 125 (CA125) can be detected by immunoassays. The CA125 epitope is used for monitoring ovarian cancer treatment progression, and has emerged as a potential target for antibody mediated immunotherapy. The extracellular tandem repeat domain of the protein is composed of repeating segments of heavily glycosylated sequence intermixed with homologous SEA (Sperm protein, Enterokinase and Agrin) domains. Here we report the purification and the first X-ray structure of a human MUC16 SEA domain. The structure was solved by molecular replacement using a Rosetta generated structure as a search model. The SEA domain reacted with three different MUC16 therapeutic antibodies, confirming that the CA125 epitope is localized to the SEA domain. The structure revealed a canonical ferredoxin-like fold, and contained a conserved disulfide bond. Analysis of the relative solvent accessibility of side chains within the SEA domain clarified the assignment of N-linked and O-linked glycosylation sites within the domain. A model of the glycosylated SEA domain revealed two major accessible faces, which likely represent the binding sites of CA125 specific antibodies. The results presented here will serve to accelerate future work to understand the functional role of MUC16 SEA domains and antibody recognition of the CA125 epitope. | ||
| + | |||
| + | Crystal structure of a human MUC16 SEA domain reveals insight into the nature of the CA125 tumor marker.,White B, Patterson M, Karnwal S, Brooks CL Proteins. 2022 Jan 17. doi: 10.1002/prot.26303. PMID:35037700<ref>PMID:35037700</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7sa9" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Brooks | + | [[Category: Brooks, C L]] |
| - | [[Category: White B]] | + | [[Category: White, B]] |
| + | [[Category: Ca125]] | ||
| + | [[Category: Mucin]] | ||
| + | [[Category: Ovarian cancer]] | ||
| + | [[Category: Pancreatic cancer]] | ||
| + | [[Category: Unknown function]] | ||
Revision as of 03:09, 21 April 2022
Human MUC16 SEA5 Domain
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