A soluble VE-cadherin fragment forms 2D arrays of dimers upon binding to a lipid monolayer
| Autor: | Danielle Gulino-Debrac, Catherine Vénien-Bryan, Jean-François Legrand, Elizabeth A. Hewat, Rana Al-Kurdi, Anne Renault, Laurence Martel |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Chemistry
Cadherin C-terminus Adhesion Crystal structure Cadherins Lipid Metabolism Protein Engineering Cell junction chemistry.chemical_compound Crystallography Microscopy Electron Monomer Structural Biology Antigens CD Chromatography Gel Molecule Humans Endothelium Vascular VE-cadherin Peptides Molecular Biology Dimerization |
| DOI: | 10.1016/j.jmb.2004.02.021 |
| Popis: | A high concentration of cadherin molecules at cell–cell adhesion sites is believed to be essential for generating strong intercellular junctions. In order to determine the interactions of cadherin domains involved in the early stages of lateral cluster formation on the cell surface, a recombinant fragment encompassing the first four domains of human VE-cadherin with a His-tag at the C terminus (VE-EC1-4-His) was produced. Two-dimensional crystals of VE-EC1-4-His were formed at the air–water interface using conventional lipids modified to contain a Ni2+-chelating group, which provides a specific site for interaction with the polyhistidine tag. The VE-EC1-4-His was monomeric at the concentration employed for crystal formation; however, the crystals exhibited a p2 symmetry and the presence of cis-dimer interactions between symmetry-related molecules. The VE-EC1-4-His molecules in the crystalline array have a remarkably compact conformation in contrast to the elongated “string of pearls” conformation seen in the hexameric assembly of VE-EC1-4-His in solution, and as seen in the crystal structure of C-cadherin. These results indicate that VE-cadherin can exist in at least two oligomeric states with different interactions between domains and can adopt highly different conformational states. We suggest that the compact cis-dimeric state may occur on isolated cells and that the compact form may serve to protect the molecule from degradation. As previously proposed we suppose that the trans-hexameric form is involved in intercellular adhesion. |
| Databáze: | OpenAIRE |
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