Abstract

Norwalk virus is the major cause of epidemic viral gastroenteritis in humans. Attempts to grow this human virus in laboratory cell lines have been unsuccessful; however, the Norwalk virus capsid protein, when expressed in insect cells infected with a recombinant baculovirus, spontaneously assembles into virus-like particles. The x-ray crystallographic structure of these recombinant Norwalk particles has been determined to 3.4 Å, using a 22-Å electron cryomicroscopy structure as a phasing model. The recombinant capsids, 380 Å in diameter, exhibit a T = 3 icosahedral symmetry. The capsid is formed by 90 dimers of the capsid protein, each of which forms an arch-like capsomere. The capsid protein has two distinct domains—a shell (S) and a protruding (P) domain—that are connected by a flexible hinge. Although the S domain has a classical β-sandwich fold, the structure of the P domain is unlike any other viral protein. One of the subdomains in the P domain formed by the most variable part of the sequence is located at the exterior of the capsid.

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