8vm1

Structural Elucidation of the Mesothelin Mucin16 CA125 Interaction

spinqualitylabelsall models 8vm1, resolution 2.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D 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. Megakaryocyte-potentiating factor (MPF) potentiates megakaryocyte colony formation in vitro. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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