The Structure of Herpesvirus Fusion Glycoprotein B-Bilayer Complex Reveals the Protein-Membrane and Lateral Protein-Protein Interaction

Glycoprotein B (gB) is a key component of the complex herpesvirus fusion machinery. We studied membrane interaction of two gB ectodomain forms and present an electron cryotomography structure of the gB-bilayer complex. The two forms differed in presence or absence of the membrane proximal region (MPR) but showed an overall similar trimeric shape. The presence of the MPR impeded interaction with liposomes. In contrast, the MPR-lacking form interacted efficiently with liposomes. Lateral interaction resulted in coat formation on the membranes. The structure revealed that interaction of gB with membranes was mediated by the fusion loops and limited to the outer membrane leaflet. The observed intrinsic propensity of gB to cluster on membranes indicates an additional role of gB in driving the fusion process forward beyond the transient fusion pore opening and subsequently leading to fusion pore expansion. [Display omitted] •Full-length gB ectodomain has a structure similar to the ectodomain lacking the MPR•The gB-bilayer structure reveals that the interaction is limited to the outer leaflet•gB trimers have an intrinsic propensity to interact laterally and form protein arrays•Arrays of gB trimers on membranes render the fusion pore open state irreversible Understanding the mechanism of membrane fusion requires structural information on fusion proteins in the context of the membrane. Maurer et al. solve a structure of herpesvirus gB bound to a membrane. The gB interacts with the membrane at the outer leaflet, which results in a protein coat or belt around the membrane.