Читать книгу Principles of Virology - Jane Flint, S. Jane Flint - Страница 192

Viral glycoproteins are integral membrane proteins firmly embedded in the lipid bilayer by a short membrane-spanning domain (Fig. 4.22). The membrane-spanning domains of viral proteins are hydrophobic α-helices of sufficient length to span the lipid bilayer. They generally separate large external domains that are decorated with oligosaccharides from smaller internal segments. The former contain binding sites for cell surface virus receptors, major antigenic determinants, and sequences that mediate fusion of viral with cellular membranes during entry. Internal domains, which make contact with other components of the virus particle, are often essential for virus assembly.

With few if any exceptions, viral membrane glycoproteins form oligomers, which can comprise multiple copies of a single protein or may contain two or more protein chains. The subunits are held together by noncovalent interactions and disulfide bonds. On the exterior of particles, these oligomers can form surface projections, often called spikes. Because of their critical roles in initiating infection, the structures of many viral glycoproteins have been determined.

The hemagglutinin (HA) protein of human influenza A virus is a trimer that contains a globular head with a top surface that is projected ~135 Å from the viral membrane by a long stem (Fig. 4.23A). The latter is formed and stabilized by the coiling of α-helices present in each monomer. The membrane-distal globular domain contains the binding site for the host cell receptor. This important functional region is located >100 Å away from the lipid membranes of influenza virus particles. Other viral glycoproteins that mediate cell attachment and entry, such as the E protein of the flavivirus tick-borne encephalitis virus, adopt a quite different orientation (and structure); the external domain of E protein is a flat, elongated dimer that lies on the surface of the viral membrane rather than projecting from it (Fig. 4.23B). Despite their lack of common structural features, the HA and the E proteins are both primed for dramatic conformational change to allow entry of internal virion components into a host cell (Chapter 5).