Fig. 5: Effect of BA.1 mutation Q954H on lipid-bound state of spike protein during fusion.

a The primary amino acid sequence of HR1 (residues N919-Q965) and HR2 (residues G1171-E1207) in bold. In the Core construct a short flexible linker sequence (SGLVPRGSG) connects the HR1 and HR2 helical repeats. The site of mutation, Glu-954 is shown in red. b Ribbon representations for the two (straight and kinked) lipid-bound conformations of HR1 that are in equilibrium and fast exchange with each other. The Q954H mutation increases the population of the kinked conformation. c Residue-specific HX rates and (d) the corresponding protection factors of HR1^WT (blue) and HR1^Q954H (red), normalized at pH 7. A protection factor of 1 (dashed line) corresponds to no protection from hydrogen exchange, i.e., no significant population of intramolecular hydrogen bonds. Data were obtained on 100 µM [¹⁵N/²H]-HR1^Q954H in the presence of 100 mM dimyristoyl phosphatidylcholine (DMPC)/dihexanoyl phosphatidylcholine (DHPC) (q ~ 0.5). Data for HR1^WT is reproduced from earlier work²⁵. e Overlay of Far-UV CD spectra of 10 µM Core in the absence (Core^WT-black and Core^Q954H-olive) in the presence of 4 M Urea (Core^WT-blue and Core^Q954H-red). f Thermal melting of Core^WT (blue) and Core^Q954H (red) as observed by CD in the presence of 4 M Urea. Melting temperatures of Core^WT and Core^Q954H are 88 °C and 90 °C, respectively.