Читать книгу Principles of Virology - Jane Flint, S. Jane Flint - Страница 240

This class is exemplified by the G protein of the rhabdovirus vesicular stomatitis virus and the gB proteins of herpesviruses. Under most conditions, the vesicular stomatitis virus G protein crystallizes as a trimer. The structural organization, shared by class III fusion proteins, is rather complex, with three domains (I to III) nested around a β-sandwich core and a long C-terminal extension (Fig. 5.19). The transition to the fusion active state consists of rotation of domains I and II and refolding of domain III to form a hairpin, similar to that described for class I fusion proteins, and projects two fusion loops toward the target membrane. In the case of vesicular stomatitis virus G protein, the trigger for fusion is acid pH. In contrast, herpesviruses carry multiple envelope proteins on their surface that might contribute to entry in different ways depending on the target cell (Fig. 5.9). It is unclear how conformational changes induced in these different surface proteins upon engagement of their various targets trigger fusion by gB.

Figure 5.19 Conformational changes in class III proteins during fusion. Structure of part of the ectodomain of vesicular stomatitis virus G protein at neutral and acid pH (PDB ID: 5I2S, 5MDM). For simplicity, only one monomer of the trimer is depicted. Domain I is colored green, domain II black, domain III orange, and domain IV (the β-sandwich core) cyan, with the two fusion loops in red. Upon exposure to acid pH, the protein flips to extend the fusion loops toward the target membrane and bring the viral membrane closer. In contrast to other fusion proteins, the conformational changes induced by acid pH in the vesicular stomatitis virus G protein are reversible in solution.