Models & Figures

	Model for fusion mediated by the influenza hemagglutinin. (1) The 'spring-loaded conformational change' repositions the fusion peptide (red). (2) The fusion peptide inserts into the target membrane. (3) Several HA trimers cluster. (4) A helix to loop transition induces a chain reversal and dimpling of the membranes. (5) Packing of the C-terminal leash (cyan) in the grooves of the coiled-coil pulls the membranes together leading to hemifusion. (6) Actions of the fusion peptide and transmembrane domain on the hemifusion diaphragm open a fusion pore. The pore expands to allow genome entry.
	Hemifusion by influenza HA. Red blood cells were labeled such that theur membranes were red and contents were green. Fusion to WT HA expressing fibroblasts labeled the cells yellow. A mutant in which 12 residues of the transmembrane domain were deleted causes hemifusion (delivery of red lipids, but not green contents). Addition of a single Arg to the truncated HA restores fusion. The figure is from Armstrong. 2000. JCB.
	Fusion subunits of class I viral fusion proteins showing the common central coiled-coil (blue). In all cases a C-helix (green) packs against the coiled-coil, but the location and length of the C-helix vary. A. Influenza HA (PDB# 1QU1). B. SIV Env (PDB# 2EZO). C. Ebola GP (PDB# 2EBO). (D) HTLV Env (PDB# 1MG1). A-C, trimers. D a monomer of the trimer. We showed that packing of the C-terminal leash (yellow in A) into the coiled-coil serves the purpose for HA as does formation of the 6HB for HIV Env.
	Influenza HA is activated by low pH, and fusion occurs in endosomes. HIV Env is activated by interactions with receptors at neutral pH, and fusion can occur at the cell surface. Avian retrovirus Env glycproteins are activated by a 2-step process: interaction with the host cell receptor, followed by exposure to low pH.
	Although Ebola virus requires low endosomal pH for fusion, it is not activated for fusion simply by exposure to low pH. Instead, Ebola requires endosomal cathepsins (that require low pH for activity) to prime the glycoprotein for subsequent fusion activation.
	ADAMs are cell surface proteins containing A Disintegrin and A Metalloprotease domain. The protease domain mediates ectodomain shedding (e.g., of cytokines and growth factors). The adhesive domains (disintegrin and cysteine-rich) may bind substrates or influence cell adhesion or cell migration. The cytoplasmic tails can interact with adapter proteins.. ADAMs have been implicated in an array of developmental (e.g. neurogenesis) and disease (e.g. arthritis) processes.