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

Area of Science:

• Structural biology
• Virology
• Molecular biology

Background:

• Human Nap1 (hNap1) is a histone chaperone crucial for chromatin dynamics.
• The HIV-1 regulatory protein Rev is essential for nuclear export of viral RNA.
• The interaction between hNap1 and Rev is functionally significant but structurally uncharacterized.

Purpose of the Study:

• To elucidate the structural basis of the hNap1-Rev interaction.
• To understand how hNap1 modulates Rev assembly and function.
• To provide molecular insights into HIV-1 replication mechanisms.

Main Methods:

• X-ray crystallography to determine hNap1 structure.
• Cryo-electron microscopy to resolve the hNap1-Rev complex structure.
• Surface plasmon resonance to quantify binding affinity.

Main Results:

• The structure reveals hNap1 binds Rev dimers via its acidic concave surface.
• hNap1 stabilizes Rev into a dimer-of-dimers tetramer, preventing aggregation.
• This interaction enhances Rev's binding to the Rev Response Element and confirms low-micromolar affinity.

Conclusions:

• hNap1 acts as a chaperone for Rev, modulating its assembly and function.
• The hNap1-Rev interaction facilitates productive engagement with viral RNA.
• This priming mechanism is crucial for efficient HIV-1 replication.