2l4g

Influenza Haemagglutinin fusion peptide mutant G13A

spinqualitylabelsall models 2l4g, 20 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2l4g is a 1 chain structure with sequence from Influenza a virus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 2jrd, 1ibn, 1xop, 1xoo Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Our previous studies showed that an angled boomerang-shaped structure of the influenza hemagglutinin (HA) fusion domain is critical for virus entry into host cells by membrane fusion. Because the acute angle of approximately 105 degrees of the wild-type fusion domain promotes efficient non-leaky membrane fusion, we asked whether different angles would still support fusion and thus facilitate virus entry. Here, we show that the G13A fusion domain mutant produces a new leaky fusion phenotype. The mutant fusion domain structure was solved by NMR spectroscopy in a lipid environment at fusion pH. The mutant adopted a boomerang structure similar to that of wild type but with a shallower kink angle of approximately 150 degrees . G13A perturbed the structure of model membranes to a lesser degree than wild type but to a greater degree than non-fusogenic fusion domain mutants. The strength of G13A binding to lipid bilayers was also intermediate between that of wild type and non-fusogenic mutants. These membrane interactions provide a clear link between structure and function of influenza fusion domains: an acute angle is required to promote clean non-leaky fusion suitable for virus entry presumably by interaction of the fusion domain with the transmembrane domain deep in the lipid bilayer. A shallower angle perturbs the bilayer of the target membrane so that it becomes leaky and unable to form a clean fusion pore. Mutants with no fixed boomerang angle interacted with bilayers weakly and did not promote any fusion or membrane perturbation. Shallow boomerang-shaped influenza hemagglutinin G13A mutant structure promotes leaky membrane fusion.,Lai AL, Tamm LK J Biol Chem. 2010 Nov 26;285(48):37467-75. Epub 2010 Sep 8. PMID:20826788 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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