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. 2021 Sep 22;118(39):e2106196118. doi: 10.1073/pnas.2106196118

Fig. 1.

Fig. 1.

Interprotomer disulfide-based stabilization of HMPV F trimer in a prefusion state. (A) Structure-based design of interprotomer disulfides based on the prefusion structure of HMPV F (PDB ID 5WB0) (26); additional designs are shown in SI Appendix, Fig. S1. (B) Properties of disulfide-stabilized prefusion HMPV Fs. Left, expression level. Right, SDS-PAGE analysis of interprotomer disulfide-stabilized HMPV F prefusion variants without (−) and with (+) reducing agent (DTT, dithiothreitol). (C) Cryo-EM 3D reconstruction at 4.8-Å resolution of the MPE33 Fab in complex with prefusion HMPV F trimer stabilized with interprotomer 84C-249C and intraprotomer 140C-147C. Density is shown in transparent cyan, with HMPV F in ribbons, colored by distance between prefusion and postfusion conformation (>5 Å, blue; <5 Å, gray, based on PDB ID 5WB0 and 5L1X); atoms for interprotomer disulfides are highlighted in red, and those for intraprotomer disulfides in magenta. (D) Close-up of prefusion residues 113 to 179 in the head region, where there is clear density showing residues 113 to 179 to be in the prefusion conformation.