FIGURE 13-20 Hemagglutinin folding and assembly. (a) Mechanism of (HA₀) trimer assembly. Transient binding of the chaperone BiP (step 1a) to the nascent polypeptide chain and of two lectins, calnexin and calreticulin, to certain oligosaccharide chains (step 1b) promotes proper folding of adjacent segments of HA₀. A total of seven N-linked oligosaccharide chains are added to the luminal portion of the nascent chain during cotranslational translocation, and PDI catalyzes the formation of six disulfide bonds per monomer. Completed HA₀ monomers are anchored in the membrane by a single membrane-spanning α helix with the N-terminus in the lumen (step 2). Interaction of three HA₀ chains with one another, initially via their transmembrane α helices, apparently triggers formation of a long stem containing one α helix from the luminal part of each HA₀ polypeptide. Finally, interactions occur among the three globular heads, generating a stable HA₀ trimer (step 3). (b) Electron micrograph (false color) of a complete influenza virion showing trimers of HA protein protruding as spikes from the surface of the viral membrane. See U. Tatu et al., 1995, EMBO J. 14:1340, and D. Hebert et al., 1997, J. Cell Biol. 139:613.

[Part (b), Chris Bjornberg/Science Source.]