Structural Basis for Dimeric Genome Selection by HIV-1

Abstract

HIV-1 selects and packages a dimeric RNA genome into assembling virions, a requirement for strand transfer-mediated recombination during reverse transcription. Conserved RNA elements within the 5'-leader that promote dimerization and packaging have been identified (dimer initiation signal, DIS; core encapsidation signal, {Psi} CES; respectively), but the molecular mechanism that couples these processes remains unknown. Using an in vitro virus assembly assay, we show that dimeric HIV-1 5'-Leader RNAs promote assembly of viral Gag proteins into protein lattices resembling those of immature virions, whereas monomeric 5'-Leader constructs with similar affinities for Gag do not. Assembly requires the cellular factor, inositol hexakisphosphate, mimicking biology. Cryogenic electron microscopy (cryoEM) and tomography (cryoTM) studies of nascent assemblies are consistent with a structural model in which the dimeric DIS2 helix bridges two elongated 6-helix bundles formed by the SP1 domains of adjacent Gag hexamers. The structure positions clusters of RNA-binding zinc knuckles from Gag's nucleocapsid domain in close proximity to clusters of conserved guanosines shown here to be essential for genome packaging. Our findings suggest that DIS2 functions as a molecular ruler, organizing Gag hexamers into structures optimized for Gag recruitment and Gag lattice expansion.

Structural basis for start codon selection by eIF5-mimic proteins
Ximena Zottig, Chun-Ying Huang, Zahra Seraj +2
Science Advances23 Oct 2026Peer-reviewedCC BYFull textMolecular biology & gene regulationCrossrefEurope PMC
Structural modelling and functional analysis support lipid binding by the dimeric E. coli DedA protein YqjA
T. J. Paige, J. Chen, A. Le Roy +9
bioRxiv20 Sep 2026PreprintCC BYFull textMolecular biology & gene regulationbioRxiv
Structural basis of endogenous inverse agonism and subtype selectivity at melanocortin receptors
X. Liu, Q. Sun, S. Zhang +2
bioRxiv3 Sep 2026PreprintAll rights reservedFull textBiophysicsbioRxiv
Structural basis of ribosomal RNA repair by RtcB2
Y. Tian, Q. Zhou, Q. Yu +5
bioRxiv3 Nov 2026PreprintAll rights reservedFull textGeneral biochemistrybioRxiv
Mechanical regulation of LINC complex function: structural basis, physiological roles, and disease mechanisms in transnuclear mechanotransduction
Shuoshuo Shao, Zhu Zhu, Huaiquan Liu
Frontiers in cell and developmental biology16 Oct 2026Peer-reviewedCC BYFull textGeneral biochemistryEurope PMC

Cite

BibTeX RIS

BibTeX

@misc{hollmann2026structural,
  title = {{Structural Basis for Dimeric Genome Selection by HIV-1}},
  author = {Nele Merret Hollmann and Siarhei Kharytonchyk and Angela Buchannan and Caela Phillips and Amir Ledbetter and Fairine Ahmed and Anna Adelstein and Kaylee Barry and Samuel A. Geleta and Cleo Burnett and Alice Telesnitsky and Barbie K. Ganser-Pornillos and Owen Pornillos and Michael F. Summers},
  howpublished = {bioRxiv},
  year = {2026},
  month = jun,
  doi = {10.64898/2026.06.17.732839},
  url = {https://www.biorxiv.org/content/10.64898/2026.06.17.732839v2},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Structural Basis for Dimeric Genome Selection by HIV-1
AU  - Nele Merret Hollmann
AU  - Siarhei Kharytonchyk
AU  - Angela Buchannan
AU  - Caela Phillips
AU  - Amir Ledbetter
AU  - Fairine Ahmed
AU  - Anna Adelstein
AU  - Kaylee Barry
AU  - Samuel A. Geleta
AU  - Cleo Burnett
AU  - Alice Telesnitsky
AU  - Barbie K. Ganser-Pornillos
AU  - Owen Pornillos
AU  - Michael F. Summers
PY  - 2026
DA  - 2026/06/17
PB  - bioRxiv
DO  - 10.64898/2026.06.17.732839
UR  - https://www.biorxiv.org/content/10.64898/2026.06.17.732839v2
AB  - HIV-1 selects and packages a dimeric RNA genome into assembling virions, a requirement for strand transfer-mediated recombination during reverse transcription. Conserved RNA elements within the 5'-leader that promote dimerization and packaging have been identified (dimer initiation signal, DIS; core encapsidation signal, {Psi} CES; respectively), but the molecular mechanism that couples these processes remains unknown. Using an in vitro virus assembly assay, we show that dimeric HIV-1 5'-Leader RNAs promote assembly of viral Gag proteins into protein lattices resembling those of immature virions, whereas monomeric 5'-Leader constructs with similar affinities for Gag do not. Assembly requires the cellular factor, inositol hexakisphosphate, mimicking biology. Cryogenic electron microscopy (cryoEM) and tomography (cryoTM) studies of nascent assemblies are consistent with a structural model in which the dimeric DIS2 helix bridges two elongated 6-helix bundles formed by the SP1 domains of adjacent Gag hexamers. The structure positions clusters of RNA-binding zinc knuckles from Gag's nucleocapsid domain in close proximity to clusters of conserved guanosines shown here to be essential for genome packaging. Our findings suggest that DIS2 functions as a molecular ruler, organizing Gag hexamers into structures optimized for Gag recruitment and Gag lattice expansion.
SN  - 2692-8205
ER  -

Abstract

Related

Cite