The CAR D1 domain forms homodimers in the crystal using the same GFCC'C" surface that interacts with the adenovirus fiber head. The homodimer is very similar to the CD2 D1-CD58 D1 heterodimer. CAR D1 also forms dimers in solution with a dissociation constant typical of other cell adhesion complexes. These results are consistent with reports that CAR may function physiologically as a homophilic cell adhesion molecule in the developing mouse brain. Adenovirus may thus have recruited an existing and conserved interaction surface of CAR to use for its own cell attachment.

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 receptorligand interactions, including those involved in intracellular signaling.

Due to a printing error, the sequence alignment in Figure 2 did not include the last two columns. The missing part contained, among others, a residue of the C″-strand important for CAR D1 dimer formation. The correct version of the figure is printed below. We apologize for any confusion caused by this error.