Universal stabilization of the influenza hemagglutinin by structure-based redesign of the pH switch regions.

ABSTRACT: For an efficacious vaccine immunogen, influenza hemagglutinin (HA) needs to maintain a stable quaternary structure, which is contrary to the inherently dynamic and metastable nature of class I fusion proteins. In this study, we stabilized HA with three substitutions within its pH-sensitive regions where the refolding starts. An X-ray structure reveals how these substitutions stabilize the intersubunit β-sheet in the base and form an interprotomeric aliphatic layer across the stem while the native prefusion HA fold is retained. The identification of the stabilizing substitutions increases our understanding of how the pH sensitivity is structurally accomplished in HA and possibly other pH-sensitive class I fusion proteins. Our stabilization approach in combination with the occasional back mu

SUBMITTER: Milder FJ 

PROVIDER: S-EPMC8833195 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature