2LWA

Conformational ensemble for the G8A mutant of the influenza hemagglutinin fusion peptide

Summary for 2LWA

• Entry DOI: 10.2210/pdb2lwa/pdb
• Related: 2KXA
• NMR Information: BMRB: 18617
• Descriptor: HEMAGGLUTININ FUSION PEPTIDE G8A MUTANT (1 entity in total)
• Functional Keywords: influenza virus, hemagglutinin, fusion peptide, g8a mutant, membrane protein
• Biological source: Influenza A virus
• Total number of polymer chains: 3
• Total formula weight: 9496.87

Authors

Lorieau, J.L.,Louis, J.M.,Schwieters, C.D.,Bax, A. (deposition date: 2012-07-26, release date: 2012-12-05, Last modification date: 2024-05-15)

Primary citation

Lorieau, J.L.,Louis, J.M.,Schwieters, C.D.,Bax, A.
pH-triggered, activated-state conformations of the influenza hemagglutinin fusion peptide revealed by NMR.
Proc.Natl.Acad.Sci.USA, 109:19994-19999, 2012

PubMed Abstract: The highly conserved first 23 residues of the influenza hemagglutinin HA2 subunit constitute the fusion domain, which plays a pivotal role in fusing viral and host-cell membranes. At neutral pH, this peptide adopts a tight helical hairpin wedge structure, stabilized by aliphatic hydrogen bonding and charge-dipole interactions. We demonstrate that at low pH, where the fusion process is triggered, the native peptide transiently visits activated states that are very similar to those sampled by a G8A mutant. This mutant retains a small fraction of helical hairpin conformation, in rapid equilibrium with at least two open structures. The exchange rate between the closed and open conformations of the wild-type fusion peptide is ~40 kHz, with a total open-state population of ~20%. Transitions to these activated states are likely to play a crucial role in formation of the fusion pore, an essential structure required in the final stage of membrane fusion.

PubMed: 23169643
DOI: 10.1073/pnas.1213801109

Experimental method

SOLUTION NMR