Dissecting the CD93-Multimerin 2 interaction involved in cell adhesion and migration of the activated endothelium
| Autor: | Paolo Toti, Alfonso Trezza, Maurizio Mongiat, Annalisa Santucci, Rosanna Pellicani, Renato V. Iozzo, Federica Nardi, Giulia Tarticchio, Federico Galvagni, Ottavia Spiga, Maurizio Orlandini, Gian Marco Tosi, Eva Andreuzzi, Elena Caldi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Models Molecular Endothelium Angiogenesis EDEN protein superfamily Biology Extracellular matrix 03 medical and health sciences Endothelial cell Cell Movement Cell Line Tumor Neoplasms medicine Cell Adhesion Human Umbilical Vein Endothelial Cells Humans CD93 Molecular Biology chemistry.chemical_classification Binding Sites Membrane Glycoproteins C1qRp Cell biology Receptors Complement Endothelial stem cell Molecular Docking Simulation 030104 developmental biology medicine.anatomical_structure chemistry Docking (molecular) Antigens Surface Mutagenesis Site-Directed Endothelium Vascular Glycoprotein Blood vessel Protein Binding |
| Popis: | The glycoprotein CD93 has recently been recognized to play an important role in the regulation of the angiogenic process. Moreover, CD93 is highly expressed in the endothelial cells of tumor blood vessel and faintly expressed in the non-proliferating endothelium. Much evidence suggests that CD93 mediates adhesion in the endothelium. Here we identify Multimerin 2 (MMRN2), a pan-endothelial extracellular matrix protein, as a specific ligand for CD93. We found that CD93 and MMRN2 are co-expressed in the blood vessels of various human tumors. Moreover, disruption of the CD93-MMRN2 interaction reduced endothelial cell adhesion and migration, making the interaction of CD93 with MMRN2 an ideal target to block pathological angiogenesis. Model structures and docking studies served to envisage the region of CD93 and MMRN2 involved in the interaction. Site-directed mutagenesis identified different residue hotspots either directly or indirectly involved in the binding. We propose a molecular model in which the coiled-coil domain of MMRN2 is engaged by F238 of CD93. Altogether, these studies identify the key interaction surfaces of the CD93-MMRN2 complex and provide a framework for exploring how to inhibit angiogenesis by hindering the CD93-MMRN2 interaction. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|