Alternative conformations of a major antigenic site on RSV F

Jones, Harrison G.; Battles, Michael B.; Lin, Chun-Chi; Bianchi, Siro; Corti, Davide; McLellan, Jason S.

The AM22 heavy chain buries 554 Å 2 (76%) on the surface of prefusion RSV F and is involved in 15 hydrogen bonds with RSV F, 14 of which are formed between the CDR H3 and seven residues within Gln202-Ser215 of α4 and the α4-α5 loop of prefusion RSV F. The light chain is responsible for the remaining 175 Å 2 (24%) of buried surface area on prefusion RSV F and forms three additional hydrogen bonds with the α4-α5 loop via the CDR L2. The high affinity and specificity of AM22 for prefusion RSV F (Fig 1 and S3 Fig) is due to the formation of a three-strand anti-parallel β-sheet between the CDR H3 of AM22 and α4-α5 loop of F1 ( Fig 2B) . When bound by AM22, the α4-helix kinks near residue Pro205 and shifts away from α5, stretching the α4-α5 loop and allowing it to adopt a β-strand conformation that pairs with the β-hairpin formed by the CDR H3 of AM22. Upon RSV F triggering and the rearrangement into the postfusion conformation, α4 and the α4-α5 loop refold into the continuous α5-helix, which would disrupt the β-sheet interaction and prevent AM22 binding.