9RMU

SIVtal integrase in complex with RNA stem-loop (focused refinement of the filament repeat unit)

Summary for 9RMU

• Entry DOI: 10.2210/pdb9rmu/pdb
• EMDB information: 54068
• Descriptor: Pol protein, RNA, ZINC ION (3 entities in total)
• Functional Keywords: integrase, rna, octamer, sivtal, viral protein
• Biological source: Simian immunodeficiency virus; More
• Total number of polymer chains: 14
• Total formula weight: 406833.37

Authors

Singer, M.R.,Cherepanov, P. (deposition date: 2025-06-18, release date: 2025-12-10, Last modification date: 2026-05-06)

Primary citation

Singer, M.R.,Li, Z.,Rey, J.S.,Hope, J.,Chenavier, F.,Cook, N.J.,Punch, E.,Smith, J.,Zhou, Z.,Maslen, S.,Masino, L.,Nans, A.,Skehel, M.,Taylor, I.A.,Zanetti, G.,Zhang, P.,Perilla, J.R.,Engelman, A.N.,Cherepanov, P.
Integrase anchors viral RNA to the HIV-1 capsid interior.
Nature, 652:1068-1075, 2026

PubMed Abstract: HIV-1 integrase (IN) promotes encapsulation of viral genomic RNA into mature viral cores, and this function is a target for ongoing antiretroviral drug development efforts. Here we determined the cryogenic electron microscopy (cryo-EM) structure of a primate lentiviral IN in a complex with RNA, revealing a linear filament made of IN octamer repeat units, each comprising a pair of asymmetric homotetramers. The assembly is stabilized through IN-RNA interactions involving mainly the IN C-terminal domains and RNA backbone. The spacing and orientation of the IN filament repeat units closely matched those of consecutive capsid (CA) hexamers within the mature CA lattice. Using cryo-EM images of native purified HIV-1 cores, we refined the structure of the IN filament as it propagates along the luminal side of the CA lattice. Each IN tetramer within the filament nestled in a CA hexamer, engaging closely with the major homology regions. Substitutions of residues involved in IN-CA contacts yielded eccentric virions with RNA nucleoids located outside of the cores. Collectively, our results establish the structural basis for the HIV-1 IN-RNA interaction and reveal that IN forms an RNA-binding module on the luminal side of the mature CA lattice.

PubMed: 41708858
DOI: 10.1038/s41586-026-10154-x

Experimental method

ELECTRON MICROSCOPY (3.3 Å)