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TitleStructural Basis for HIV-1 Rev Recognition by the Histone Chaperone Human Nap1.
Journal, issue, pagesJ Biol Chem, Page 113120, Year 2026
Publish dateMay 6, 2026
AuthorsElif Eren / Norman R Watts / Dennis C Winkler / Paul T Wingfield /
PubMed AbstractHuman Nap1 (hNap1) is a histone chaperone involved in chromatin dynamics and has been shown to interact with the HIV-1 regulatory protein Rev, which is essential for nuclear export of viral RNA. ...Human Nap1 (hNap1) is a histone chaperone involved in chromatin dynamics and has been shown to interact with the HIV-1 regulatory protein Rev, which is essential for nuclear export of viral RNA. Despite the functional significance of this interaction, its structural basis has remained elusive. Here, we present the X-ray crystal structure of hNap1 and the cryo-electron microscopy structure of the core domain of hNap1-Rev complex. The structure reveals that hNap1 binds Rev dimers via its acidic concave surface, engaging the Rev arginine-rich motif and oligomerization domain, and stabilizes Rev as a dimer-of-dimers tetramer. This interaction prevents higher-order Rev aggregation and enhances Rev's cooperative binding to the Rev Response Element. Surface plasmon resonance measurements confirm the formation of a stable complex with an apparent low-micromolar affinity between hNap1 and Rev, supporting a chaperone-like, reversible association. Our findings provide molecular insight into how hNap1 modulates Rev assembly and function, suggesting a model in which hNap1 primes Rev for productive engagement with viral RNA, thereby facilitating HIV-1 replication.
External linksJ Biol Chem / PubMed:42103228
MethodsEM (single particle) / X-ray diffraction / EM (helical sym.)
Resolution3.2 - 8.3 Å
Structure data

EMDB-75601, PDB-11bc:
Human Nap1 in complex with HIV-1 Rev
Method: EM (single particle) / Resolution: 3.3 Å

PDB-11bd:
human nucleosome assembly protein 1 (human Nap1)
Method: X-RAY DIFFRACTION / Resolution: 3.2 Å

PDB-11be:
HIV-1 Rev Filament
Method: ELECTRON MICROSCOPY / Resolution: 8.3 Å

Source
  • homo sapiens (human)
  • human immunodeficiency virus 1
KeywordsCHAPERONE / histone chaperone / H2A-H2B / Nap1 / HIV-1 Rev / Nucleosome assembly protein 1 / Nucleosome assembly protein like 1 / Histone / VIRAL PROTEIN / HIV-1 / Rev / Filament / Rev Response Element / RNA / RNA binding protein

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