2L4G

Influenza Haemagglutinin fusion peptide mutant G13A

Summary for 2L4G

• Entry DOI: 10.2210/pdb2l4g/pdb
• Related: 1IBN 1XOO 1XOP 2JRD
• NMR Information: BMRB: 17240
• Descriptor: Haemagglutinin (1 entity in total)
• Functional Keywords: fusion peptide, viral protein
• Biological source: Influenza A virus
• Total number of polymer chains: 1
• Total formula weight: 2802.28

Authors

Lai, A.L.,Tamm, L.K. (deposition date: 2010-10-05, release date: 2010-10-20, Last modification date: 2024-05-01)

Primary citation

Lai, A.L.,Tamm, L.K.
Shallow boomerang-shaped influenza hemagglutinin G13A mutant structure promotes leaky membrane fusion.
J.Biol.Chem., 285:37467-37475, 2010

PubMed Abstract: 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 ∼105° 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 ∼150°. 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.

PubMed: 20826788
DOI: 10.1074/jbc.M110.153700

Experimental method

SOLUTION NMR