9BW9

Tetrameric Complex of full-length HIV-1 integrase protein bound to the integrase binding domain of LEDGF/p75

Summary for 9BW9

• Entry DOI: 10.2210/pdb9bw9/pdb
• EMDB information: 44962
• Descriptor: PC4 and SFRS1-interacting protein, Integrase (2 entities in total)
• Functional Keywords: viral protein, protein complex, hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 183618.03

Authors

Jing, T.,Shan, Z.,Lyumkis, D.,Biswas, A. (deposition date: 2024-05-21, release date: 2025-06-25, Last modification date: 2025-11-05)

Primary citation

Jing, T.,Shan, Z.,Dinh, T.,Biswas, A.,Jang, S.,Greenwood, J.,Li, M.,Zhang, Z.,Gray, G.,Shin, H.J.,Zhou, B.,Passos, D.,Strutzenberg, T.S.,Aiyer, S.,Andrade, L.,Zhang, Y.,Li, Z.,Craigie, R.,Engelman, A.N.,Kvaratskhelia, M.,Lyumkis, D.
Oligomeric HIV-1 integrase structures reveal functional plasticity for intasome assembly and RNA binding.
Nat Commun, 16:9430-9430, 2025

PubMed Abstract: Integrase (IN) performs dual essential roles during HIV-1 replication. During ingress, IN functions within an oligomeric "intasome" assembly to catalyze viral DNA integration into host chromatin. During late stages of infection, tetrameric IN binds viral RNA and orchestrates the condensation of ribonucleoprotein complexes into the capsid core. The molecular architectures of HIV-1 IN assemblies that mediate these distinct events remain unknown. Furthermore, the IN tetramer is an important antiviral target for investigational allosteric IN inhibitors. Here, we determined cryo-EM structures of wildtype HIV-1 IN tetramers and intasome hexadecamers. Our structures unveil a remarkable plasticity that leverages IN C-terminal domains and abutting linkers to assemble functionally distinct oligomeric forms. Alteration of a newly recognized conserved interface revealed that both IN functions track with tetramerization in vitro and during HIV-1 infection. Collectively, our findings reveal how IN plasticity orchestrates its diverse molecular functions and suggest a working model for IN-viral RNA binding. Moreover, our structure of the IN tetramer provides atomic blueprints for the rational development of improved allosteric inhibitors.

PubMed: 41136407
DOI: 10.1038/s41467-025-64479-8

Experimental method

ELECTRON MICROSCOPY (4.1 Å)