8vm1

From Proteopedia

(Difference between revisions)

Current revision

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: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
↑ 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 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8vm1"

Categories: Homo sapiens | Large Structures | Rupert PB | Strong R

@@ 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

From Proteopedia

Current revision

Structural Elucidation of the Mesothelin Mucin16 CA125 Interaction

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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