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Kinetic analysis of adenovirus fiber binding to its receptor reveals an avidity mechanism for trimeric receptor-ligand interactions



Kinetic analysis of adenovirus fiber binding to its receptor reveals an avidity mechanism for trimeric receptor-ligand interactions



Journal of Biological Chemistry 276(12): 9009-9015



Most adenoviruses bind to the N-terminal immunoglobulin domain D1 of the coxsackievirus and adenovirus receptor via the head part of their fiber proteins. Three receptor molecules can bind per fiber head. We expressed the D1 domain and the adenovirus type 2 fiber head in bacteria and studied binding interactions by surface plasmon resonance measurements. When receptor domains bind adenovirus fiber independently of each other, the dissociation constant is 20-25 nM. However, when adenovirus fiber binds to receptors immobilized on the sensor chip, a situation better mimicking adenovirus binding to receptors on the cell surface, the dissociation constant was around 1 nM. Kinetic analysis shows that this happens via an avidity mechanism; three identical interactions with high on and off rate constants lead to tight binding of one fiber head to three receptor molecules with a very low overall off rate. The avidity mechanism could be used by other viruses that have multimeric adhesion proteins to attach to target cells. It could also be more general to trimeric receptor-ligand interactions, including those involved in intracellular signaling.

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Accession: 003486774

Download citation: RISBibTeXText

PMID: 11124261

DOI: 10.1074/jbc.M009304200



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