2lwa

Publication Abstract from PubMed

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 approximately 40 kHz, with a total open-state population of approximately 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.

pH-triggered, activated-state conformations of the influenza hemagglutinin fusion peptide revealed by NMR.,Lorieau JL, Louis JM, Schwieters CD, Bax A Proc Natl Acad Sci U S A. 2012 Nov 19. PMID:23169643^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.