| Title: |
Integrase anchors viral RNA to the HIV-1 capsid interior |
| Authors: |
Singer, Matthew R.; Li, Zhen; Rey, Juan S; Hope, Joshua; Chenavier, Florian; Cook, Nicola J.; Punch, Emma; Smith, Jamie; Zhou, Zhiyu; Maslen, Sarah; Masino, Laura; Nans, Andrea; Skehel, Mark; Taylor, Ian A.; Zanetti, Giulia; Zhang, Peijun; Perilla, Juan R.; Engelman, Alan N.; Cherepanov, Peter |
| Publisher Information: |
Nature |
| Publication Year: |
2026 |
| Collection: |
The University of Delaware Library Institutional Repository |
| Description: |
This article was originally published in Nature. The version of record is available at: https://doi.org/10.1038/s41586-026-10154-x Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. ; 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 efforts1,2,3. 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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://udspace.udel.edu/handle/19716/36925 |
| Availability: |
https://udspace.udel.edu/handle/19716/36925 |
| Rights: |
Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.F4CDBF34 |
| Database: |
BASE |