Hemagglutinin stalk region (HA stalk (for influenza HA); HN stalk (for paramyxovirus hemagglutinin-neuraminidase protein))

The Hemagglutinin stalk region is the conserved, lower segment of the viral HA glycoprotein, underlying the variable globular head that mediates receptor binding. In influenza virus, the HA stalk consists of a coiled-coil structure that supports the trimeric HA architecture, stabilizes the protein, and transduces pH-dependent conformational changes to trigger fusion of the viral and cellular membranes during entry. The stalk domain is highly conserved compared to the immunodominant head, making it a prime target for broadly neutralizing monoclonal antibodies and "universal" vaccine approaches. Therapeutic targeting of the stalk region offers the potential for protection against multiple influenza strains and subtypes due to its functional constraints and low mutation tolerance. Similar stalk regions in hemagglutinin-neuraminidase proteins of paramyxoviruses mediate interaction with fusion proteins and play equivalent structural and functional roles.

Other names

HA stalkHemagglutinin-neuraminidase stalk (for paramyxoviruses)Attachment protein stalk regionFusion domain (occasionally for the fusion-active region)

Antibody-mediated neutralization: Antibodies bind the stalk, block conformational rearrangements necessary for membrane fusion. Vaccination: Elicitation of anti-stalk antibodies conferring broad influenza protection.