Structural highlights
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
