Viral membrane fusion - PubMed (original) (raw)

Review

Viral membrane fusion

Stephen C Harrison. Virology. 2015 May.

Abstract

Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a "fusion loop" or "fusion peptide") engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics.

Keywords: Fusion mechanism; Fusion protein; Virus entry.

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Figures

Figure 1

Steps in fusion of two lipid bilayers. Apposed leaflets in blue; distal leaflets in brown.

Figure 2

Pre- and postfusion structures (left and right, respectively) of representative fusion-proteins from each of the three known classes, with approximate positions of membrane shown. A. Class I: influenza virus HA ectodomain (Protein Databank entries 2YPG and 1QU1 for pre- and postfusion forms of the ectodomain, respectively). HA1 chains in shades of red/gold and HA2 chains in shades of blue (paired as red-blue, gold-cyan, dark red-marine blue). The N terminus of HA1 and the C-terminus of the HA2 ectodomain are labeled. Blue arrow: position of fusion peptides inserted near threefold axis in prefusion form. Only HA2 is shown on the right. The N-terminus (blue arrow; note that the fusion peptide is not part of the structure shown) and C-terminus of the cyan-colored subunit are indicated. B. Class II: dengue virus type 2 E protein (3J27, 1OAN and 1OK8). The tangential (“side”) view shows a dimer of the complete E polypeptide chain and the M polypeptide chain from the cryoEM model (3J27); the radial (“top”) view shows just the “stem-less” ectodomain (1OAN). Colors: domain I: red; domain II: yellow; domain III: blue; stem: cyan; transmembrane anchor: slate; M: orange. Colors for domains I, II and III are the same in the postfusion representation. A dashed cyan arrow on the postfusion trimer shows where the stem emerges from domain III. Red asterisks: fusion loops. Class III: VSV G ectodomain (2J6J and 2CMZ). The three chains are in red, blue, and magenta. Dashed lines show the location of a disordered, C-terminal segment that connects the folded protein to the transmembrane anchor. Only the red-subunit C-terminal segment is shown on the right. The curve red arrow indicates that in the transition from the conformation on the left to the conformation one the right, the domain bearing the fusion loops flips over by about 180° to engage the host-cell membrane. Red asterisks: fusion loops. Figure made with Pymol (Schrödinger).

Figure 3

Schematic diagram of stages of influenza virus fusion. (1) Receptor attachment. (2) Separation of HA1 heads triggered by reduced pH. (3) Extended intermediate. (Only HA2 shown, although HA1 remains tethered to it through a disulfide bond.) Fusion peptides engage the target membrane. Arrows show incipient folding back of the coiled-coil. (4) Hemifusion induced by refolding of HA2. (5) Final refolding steps stabilize nascent fusion pore.

Figure 4

Schematic diagram of stages of dengue virus fusion (modified from [62]).

Figure 5

Comparison of fusion as catalyzed by influenza virus HA, SNAREs, flavivirus E protein (modified from [83]).

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Viral membrane fusion - PubMed (original) (raw)