Work

Structural basis for HIV-1 Rev recognition by the histone chaperone human Nap1

Year: 2026

Type: article

Abstract: 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.

Source: Journal of Biological Chemistry

DOI: 10.1016/j.jbc.2026.113120

Authors: Elif Eren, Norman R. Watts, Dennis C. Winkler, Paul T. Wingfield

Institutions: National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute on Deafness and Other Communication Disorders

Language: English

Topic: HIV Research and Treatment

Subfield: Virology

Field: Immunology and Microbiology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,430