Influenza hemagglutinin is spring-loaded by a metastable native conformation

摘要

Enveloped viruses enter cells by protein- mediated membrane fusion. For influenza virus, membrane fusion is regulated by the conformational state of the hem- agglutinin (HA) protein, which switches from a native (non- fusogenic) structure to a fusion-active (fusogenic) conforma- tion when exposed to the acidic environment of the cellular endosome. Here we demonstrate that destabilization of HA at neutral pH, with either heat or the denaturant urea, triggers a conformational change that is biochemically indistinguish- able from the change triggered by low pH. In each case, the conformational change is coincident with induction of mem- brane-fusion activity, providing strong evidence that the fu- sogenic structure is formed.