Intermediate conformations during viral fusion glycoprotein structural transition

•Three classes of fusion glycoproteins have been hitherto identified.•Structures of their pre-fusion and post-fusion states have revealed a huge conformational change.•Intermediate structures during the structural transition have been recently characterized.•Published data are consistent with the existence of a ‘pre-hairpin’ intermediate.

Entry of enveloped viruses into cells requires the fusion of viral and cellular membranes, driven by conformational changes in viral glycoproteins. Three different classes of viral fusion proteins have been hitherto identified based on common structural elements. Crystal structures have provided static pictures of pre-fusion and post-fusion conformations of these proteins and have revealed the dramatic reorganization of the molecules, but the transition pathway remains elusive. In this review, we will focus on recent data aiming to characterize intermediate structures during the conformational change. All these data support the existence of a pre-hairpin intermediate, but its oligomeric status is still a matter of debate.