Structural Basis of Mammalian Orthoreovirus Cell Attachment
Pierre Schelling, Jacquelyn A. Campbell, Thilo Stehle and Terence S. Dermody
from: Segmented Double-stranded RNA Viruses: Structure and Molecular Biology (Edited by: John T. Patton). Caister Academic Press, U.K. (2008)
Abstract
Mammalian orthoreoviruses are nonenveloped viruses that display strain-specific disease phenotypes following infection of newborn mice. In several cases, these differences in disease expression segregate genetically with the viral attachment protein, σ1. The homotrimeric σ1 protein is an elongated fiber with an N-terminal tail topped with a C-terminal head. A domain in the tail of serotype 3 σ1 binds to α-linked sialic acid, whereas the head domain binds to junctional adhesion molecule-A (JAM-A). The crystal structure of a C-terminal region of σ1 has significantly advanced our understanding of several important properties of this protein, such as its multimeric state, its conformational dynamics, and its interaction with receptors sialic acid and JAM-A. The analysis of repetitive motifs in the crystallized fragment also has served to approximate key parameters of the full-length protein, such as its overall structure and flexibility. Furthermore, numerous structural and functional relationships between σ and the adenovirus attachment protein, fiber, have suggested an evolutionary link in the receptor-binding strategies of these two viruses. The existence of such a link is also supported by structural and functional similarities shared by the σ1 receptor JAM-A and the coxsackievirus and adenovirus receptor (CAR). Both JAM-A and CAR contain two immunoglobulin-like domains, form homodimers at regions of cell-cell contact, and contain sequences in their cytoplasmic tails that anchor the proteins to the actin cytoskeleton. It thus appears that the strategy for attachment and entry of reovirus is less similar to other members of the Reoviridae family and more similar to that of adenovirus read more ...
