Schematic representation of M2 domains and conservation of a putative caveolin-1 binding domain in human influenza A viruses. A. For reasons of clearness, only a M2 monomer is indicated in the drawing. M2 tetramers function as an ion-pump (residing in a helical domain in the transmembrane region represented by cylinder 1). The C-terminal region is important for virus assembly and budding. A palmitoyl residue (jigsaw line) is linked to cysteine 50. The caveolin-1 binding domain resides in the loop and helical domain (cylinder 2) tilted perpendicularly with respect to the TM domain and is supposed to face the inner leaflet of the membrane. B. Conservation of a putative caveolin-1 binding domain. The core motif of the caveolin-1 binding domain (bold letters F 47, Y 52, F 55) is highly conserved among most subtypes of human influenza A viruses (insert). C. Alignment of M2 (H1N1) sequences. The putative CBD core (bold) and adjacent sequences of influenza A viruses of pandemic H1N1 strains (2009 USA/Mexico, 1977 'Russian flu', 1918 'Spanish flu') were aligned to the M2 region (aa 41-65) of the Puerto Rico strain 8/1934. Conserved residues: asterisks *. Amino acid deviations: faint red.