Fig. 2: The structure of full-length IN reveals conformational rearrangements and inter-domain interactions.

a Comparison of the CCD-CTD dimer from the IN tetramer to previously determined two-domain IN structures from HIV-1 or other lentiviruses. All prior structures are colored in gray and correspond to HIV-1 (1EX4⁶⁴ and 5HOT³⁷), MVV (5T3A)¹⁰, or SIV (1C6V⁶⁵). b Comparison of a single CCD-CTD protomer from the IN tetramer to individual fully modeled IN protomers from the MVV intasome¹⁰. The conformation of the CCD-CTD protomer from HIV-1 is distinct from all modeled MVV conformations, implying a large degree of structural plasticity. A single CCD-CTD protomer from the IN tetramer is colored in gray. c The structure of the tetramer is displayed in the center, with key interaction interfaces shown within inset panels. The interaction mediated by the central CTD:CTD dimer (bottom left panel) resides in an anti-parallel configuration, which is distinct from the parallel configuration previously encountered in CCD-CTD oligomeric assemblies with bound ALLINIs³⁷ or within dimeric CTD:CTD structures in solution⁶⁶ (shown in gray, PDB: 1IHV), but resembles the crystal packing interactions observed in a recent ALLINI-bound structure (PDB: 8CTA)⁶⁷ shown in light sea green. The CTD also mediates other diverse interactions, including with the NTD (upper left) and with the CCD-CTD linker (upper right) within the IN tetramer.