File:Fmicb-11-01063-g005.jpg

English: FIGURE 5. The structures of HSV gH and gB protein in the native and fusion-intermediate states, which serve as sources of protein- and peptide-based HSV inactivators. (A) Schematic representation of HSV-1 gH and gB composition. gH is composed of the ectodomain (H1, H2, and H3 domains, colored mazarine blue, green, and yellow, respectively), transmembrane domain (TM) and cytoplasmic tail (CP). gB is composed of domains I–V, transmembrane region (TM) and cytoplasmic domain (CP). (B) The HSV entry process orchestrated by a set of glycoproteins, including receptor-binding gD, fusion-regulating gH/gL and the fusogen gB. gD binding to either receptor, such as HVEM and nectin-1, causes its conformational change to expose the profusion domain. gB may also bind to specific cell receptors, such as (PILR)α and NMHC-II. Meanwhile, gH/gL may be facilitated by the activated form of gD to convert into a form able to interact with gB, triggering the transformation of the prefusion form of gB into a fusogenic state. Next, Akt (protein kinase B) may be triggered to translocate to the outer leaflet microdomains of the plasma membrane to interact with gB, which further induces Akt phosphorylation and intracellular calcium release. Subsequently gB inserts the fusion loop into the target cell membrane to form the extended, trimeric intermediate, which allows fusion of the two membranes. The pre-fusion conformation of gH/gL and gB are highlighted in a green box, which is shown in more detail in (C). (C) Side view of the pre-fusion conformation of the native gH/gL complex (modified from PDB ID: 3M1C) and gB (modified from PDB ID: 5FZ2). Names and sequences of inactivators are listed in the three boxes, and the arrows depict their positions on gH/gL and gB. Target sites of these inactivators have not been defined clearly, thus not shown here.