8vm1: Difference between revisions

Latest revision as of 05:38, 4 September 2024

Structural Elucidation of the Mesothelin Mucin16 CA125 Interaction

Structural highlights

8vm1 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.65Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MSLN_HUMAN Antibodies against MSLN are detected in patients with mesothelioma and ovarian cancer.

Function

MUC16_HUMAN Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces.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 (MSLN) is a cell-surface glycoprotein expressed at low levels on normal mesothelium but overexpressed in many cancers. Mesothelin has been implicated to play role/s in cell adhesion and multiple signaling pathways. Mucin-16/CA125 is an enormous cell-surface glycoprotein, also normally expressed on mesothelium and implicated in the progression and metastasis of several cancers, and directly binds mesothelin. However, the precise biological function/s of mesothelin and mucin-16/CA125 remain mysterious. We report protein engineering and recombinant production, qualitative and quantitative binding studies, and a crystal structure determination elucidating the molecular-level details governing recognition of mesothelin by mucin-16/CA125. The interface is small, consistent with the approximately micromolar binding constant and is free of glycan-mediated interactions. Sequence comparisons and modeling suggest that multiple mucin-16/CA125 modules can interact with mesothelin through comparable interactions, potentially generating a high degree of avidity at the cell surface to overcome the weak affinity, with implications for functioning and therapeutic interventions.

Structural elucidation of the mesothelin-mucin-16/CA125 interaction.,Rupert PB, Buerger M, Friend DJ, Strong RK Structure. 2024 Aug 8;32(8):1049-1054.e2. doi: 10.1016/j.str.2024.04.011. Epub , 2024 May 3. PMID:38703776^[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:https://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:https://dx.doi.org/10.1074/jbc.M312372200
↑ Rupert PB, Buerger M, Friend DJ, Strong RK. Structural elucidation of the mesothelin-mucin-16/CA125 interaction. Structure. 2024 Aug 8;32(8):1049-1054.e2. PMID:38703776 doi:10.1016/j.str.2024.04.011

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OCA

[1] 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

[2] 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:https://dx.doi.org/10.1074/jbc.M312372200

[3] 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

[4] 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:https://dx.doi.org/10.1074/jbc.M312372200

[5] Rupert PB, Buerger M, Friend DJ, Strong RK. Structural elucidation of the mesothelin-mucin-16/CA125 interaction. Structure. 2024 Aug 8;32(8):1049-1054.e2. PMID:38703776 doi:10.1016/j.str.2024.04.011

[1]

[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8vm1 is ON HOLD
+==Structural Elucidation of the Mesothelin Mucin16 CA125 Interaction==
+<StructureSection load='8vm1' size='340' side='right'caption='[[8vm1]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8vm1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8VM1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VM1 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.65&#8491;</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=8vm1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vm1 OCA], [https://pdbe.org/8vm1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vm1 RCSB], [https://www.ebi.ac.uk/pdbsum/8vm1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vm1 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/MSLN_HUMAN MSLN_HUMAN] Antibodies against MSLN are detected in patients with mesothelioma and ovarian cancer.
+== 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.[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;">
+== Publication Abstract from PubMed ==
+Mesothelin (MSLN) is a cell-surface glycoprotein expressed at low levels on normal mesothelium but overexpressed in many cancers. Mesothelin has been implicated to play role/s in cell adhesion and multiple signaling pathways. Mucin-16/CA125 is an enormous cell-surface glycoprotein, also normally expressed on mesothelium and implicated in the progression and metastasis of several cancers, and directly binds mesothelin. However, the precise biological function/s of mesothelin and mucin-16/CA125 remain mysterious. We report protein engineering and recombinant production, qualitative and quantitative binding studies, and a crystal structure determination elucidating the molecular-level details governing recognition of mesothelin by mucin-16/CA125. The interface is small, consistent with the approximately micromolar binding constant and is free of glycan-mediated interactions. Sequence comparisons and modeling suggest that multiple mucin-16/CA125 modules can interact with mesothelin through comparable interactions, potentially generating a high degree of avidity at the cell surface to overcome the weak affinity, with implications for functioning and therapeutic interventions.
-Authors: Rupert, P.B., Strong, R.
+Structural elucidation of the mesothelin-mucin-16/CA125 interaction.,Rupert PB, Buerger M, Friend DJ, Strong RK Structure. 2024 Aug 8;32(8):1049-1054.e2. doi: 10.1016/j.str.2024.04.011. Epub , 2024 May 3. PMID:38703776<ref>PMID:38703776</ref>
-Description: Structural Elucidation of the Mesothelin Mucin16 CA125 Interaction
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Rupert, P.B]]
+<div class="pdbe-citations 8vm1" style="background-color:#fffaf0;"></div>
-[[Category: Strong, R]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Rupert PB]]
+[[Category: Strong R]]

8vm1: Difference between revisions

Latest revision as of 05:38, 4 September 2024

Structural Elucidation of the Mesothelin Mucin16 CA125 Interaction

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

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