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Structural and Mechanistic Studies of Measles Virus Illuminate Paramyxovirus Entry

Figure 1

Measles virus fusion model.

(Left panel) Model representation of the MeV envelope glycoprotein prefusion hetero-oligomer. The H and F complexes are aligned in a staggered head configuration in which the F head is thought to stand in contact with the H stalk [33], [57]. (Middle and right panels) Hypothetical dissociation model of F triggering. Upon binding to the cellular receptor, H and F dissociate, resulting in triggering of major conformational changes in metastable prefusion F. Refolding into the stable postfusion conformation is considered to occur through a series of intermediate conformations, including a hypothetical pre-hairpin intermediate [13], [56]. Likely, refolding of multiple F complexes is required to open a fusion pore and enable viral entry. For improved clarity, MeV H is represented as a single tetramer, and F as a single trimer in the hetero-oligomeric fusion complex. More than one F trimer may interact, however, with each individual H tetramer. The insert shows an enlarged representation of proposed lipid mixing intermediates. As F refolds, first the outer membranes are thought to fuse, creating a lipid stalk. Membrane merger is then thought to advance through hemifusion to pore formation. For clarity, F complexes have been eliminated from the lipid mixing representations. Structural renderings are based on original crystal structures (form I H head domains as in [31]), homology models of MeV F [55], [58] based on coordinates reported for pre- and post-fusion PIV5 and PIV3 F, respectively [56], [59], or hypothetical structural models (F pre-hairpin intermediate). H stalk domains are modeled in an assumed α-helical configuration [33]. High-resolution structural models were aligned at the level of the transmembrane domain (viral envelope) and then morphed into low resolution images using the Sculptor (resolution 12, voxel size 3) package [60].

Figure 1

doi: https://doi.org/10.1371/journal.ppat.1002058.g001