Fig. 7.

Low-resolution model of the SPRY–capsid interaction. (a) HIV capsid contains two independently folded domains CA-NTD and CA-CTD connected by a flexible linker. The CA-CTD-mediated dimerization and CA-NTD-mediated hexamerization are two major interfaces formed in the hexagonal-like assembly of the capsid in the mature viral core. (b) All the epitopes recognized by the SPRY domain are located within the CA-NTD. Our data suggest that there are several distinct and possibly overlapping CA-NTD epitopes that the SPRY can possibly bind to. (c) Dimerization of CA-WT can mimic relative orientation of two CA-NTDs located in the neighboring hexamers within the assembled core. Binding of the SPRY domain to CA-WT involves the v1 loop and has higher affinity than binding to the isolated CA-NTD. (d) Isolated capsid hexamers (CA-HEX) produced by disulfide cross-linking of the CA-NTD (yellow bars) and by disruption of the CA-CTD dimerization interface (red stars) binds to the SPRY with higher affinity than CA-NTD, but the binding does not involve the v1 loop. (e) Our data are best explained by a binding model that positions the SPRY domain over the interhexamer gap with the v1 loop spanning the gap. (f) Alternative model to account for the lack of v1 involvement in binding to CA-HEX. v1 may interact with capsid surfaces that are no longer accessible in the cross-linked hexamer.