Fig. 7: Mutations that modulate acid stability localize to pH-responsive regions in a subtype-specific way.
From: Host switching mutations in H5N1 influenza hemagglutinin suppress site-specific activation dynamics
A Peptides that exhibit dynamic differences upon acidification for H5 (Viet04 WT, Indo05 WT, Colo22; PDB 4BGW), H1 (Puerto Rico/1934; PDB 1RU7), and H3 (Aichi/1968; PDB 6Y5G) are colored purple. B Mutations that modulate HA acid stability are shown in green6,13,14,42,49,52,53,54,55,56,57,58,59,60. For H5, dynamics and acid shifting mutations fall within the HA stalk and fusion peptide proximal region as well as in the F’ and vestigial esterase E’ domain including contact sites with the apex of the HA2 C-helix bundle (see structural motif annotations in Fig. 2A). For H1 HA, mutations at the HA1-HA1 interface are seen, which also undergoes dynamic uncaging22 as well as in the HA stalk A-helix region and stalk base. By contrast, in H3 HA, the HA1-HA1 interactions remain stable and become more ordered approaching the threshold of activation22,25, but dynamics and acid stabilizing mutations cluster around the HA2 stalk regions, which respond first to low pH.
