Figure 4

Alignment of the H3 hemagglutinin (HA) trimer with the neck and carbohydrate recognition domains (NCRD) of an SP-D trimer. (A) The structure of X31 H3N2 complexed with (a2-3) sialyllactose (red sticks) [38] was aligned with that of the N-terminal carbohydrate recognition domain (NCRD) of SP-D complexed with maltose [40] using Accelrys DS Visualizer 1.7. The distance between the C1 atom of one glucose unit of maltose (dark magenta sticks) and the corresponding Ca atom of position 133 or 144 (light magenta balls) was within 18 to 20 Angstroms for all three monomeric interactions. This distance can be covered by an asparagine side chain plus three or more glycan units, suggesting that a glycan originating from either position 133 or 144 of HA can fit into the glycan binding pocket of SP-D and simultaneous interaction by all three monomers are possible. The Ca atoms of position 122 (purple balls) are too far (~30 angstroms) from the corresponding the C1 atoms of glucose units bound to SP-D, and unlike positions 133 and 144, the path of 122 to that glucose is blocked by a fold in the hemagglutinin structure. Each monomer of HA and SP-D is shown as ribbons with different colors matching each monomeric interaction. (B) The side view of the aligned HA and SP-D trimers in (A) was turned approximately 90 degrees to generate an axial view from the SP-D stem in which the trimeric hemagglutinin is shown as white ribbons while the trimeric SP-D is depicted as green ribbons. Binding by SP-D to the glycans originating at the Ca atoms at position 133 or 144 (light magenta balls) of hemagglutinin would completely block the ability of HA to bind to cellular sialic acid targets (red sticks). Alignment of the H1 hemagglutinin based on its positions 144 and 172 onto the NCRD of SP-D yielded similar conclusions.