2DCI

NMR structure of influenza HA fusion peptide mutant W14A in DPC in pH5

Summary for 2DCI

• Entry DOI: 10.2210/pdb2dci/pdb
• Related: 1IBN 1IBO 1XOO 1XOP
• NMR Information: BMRB: 6954
• Descriptor: Hemagglutinin (1 entity in total)
• Functional Keywords: ha, fusion peptide, viral protein
• Cellular location: Virion membrane; Single-pass type I membrane protein (Potential): P11134
• Total number of polymer chains: 1
• Total formula weight: 1939.15

Authors

Tamm, L.K.,Lai, A.L. (deposition date: 2006-01-07, release date: 2006-01-24, Last modification date: 2024-05-29)

Primary citation

Lai, A.L.,Park, H.,White, J.M.,Tamm, L.K.
Fusion peptide of influenza hemagglutinin requires a fixed angle boomerang structure for activity
J.Biol.Chem., 281:5760-5770, 2006

PubMed Abstract: The fusion peptide of influenza hemagglutinin is crucial for cell entry of this virus. Previous studies showed that this peptide adopts a boomerang-shaped structure in lipid model membranes at the pH of membrane fusion. To examine the role of the boomerang in fusion, we changed several residues proposed to stabilize the kink in this structure and measured fusion. Among these, mutants E11A and W14A expressed hemagglutinins with hemifusion and no fusion activities, and F9A and N12A had no effect on fusion, respectively. Binding enthalpies and free energies of mutant peptides to model membranes and their ability to perturb lipid bilayer structures correlated well with the fusion activities of the parent full-length molecules. The structure of W14A determined by NMR and site-directed spin labeling features a flexible kink that points out of the membrane, in sharp contrast to the more ordered boomerang of the wild-type, which points into the membrane. A specific fixed angle boomerang structure is thus required to support membrane fusion.

PubMed: 16407195
DOI: 10.1074/jbc.M512280200

Experimental method

SOLUTION NMR