Interaction of coxsackievirus B3 with the full length coxsackievirus-adenovirus receptor

Group B coxsackieviruses (CVB) utilize the coxsackievirus-adenovirus recept or (CAR) to recognize host cells. CAR is a membrane protein with two Ig-lik e extracellular domains (D1 and D2), a transmembrane domain and a cytoplasm ic domain. The three-dimensional structure of coxsackievirus B3 (CVB3) in c omplex with full length human CAR and also with the D1D2 fragment of CAR we re determined to similar to 22 Angstrom resolution using cryo-electron micr oscopy (cryo-EM). Pairs of transmembrane domains of CAR associate with each other in a detergent cloud that mimics a cellular plasma membrane. This is the first view of a virus-receptor interaction at this resolution that inc ludes the transmembrane and cytoplasmic portion of the receptor. CAR binds with the distal end of domain D1 in the canyon of CVB3, similar to how othe r receptor molecules bind to entero- and rhinoviruses. The previously descr ibed interface of CAR with the adenovirus knob protein utilizes aside surfa ce of D1.