Structural basis for cooperative RNA binding and export complex assembly by HIV Rev.

Area of Science:

• Molecular Biology
• Virology
• Structural Biology

Background:

• HIV replication depends on nuclear export of unspliced viral RNAs.
• The Rev protein mediates this export by binding to the Rev response element (RRE) RNA.
• This binding forms a specific ribonucleoprotein (RNP) complex that interacts with the host export factor Crm1.

Purpose of the Study:

• To elucidate the structural basis of Rev protein's cooperative binding to RRE RNA.
• To understand how Rev protein oligomerization contributes to RRE specificity and Crm1 interaction.
• To reveal the mechanism by which Rev facilitates efficient viral RNA export.

Main Methods:

• X-ray crystallography was used to determine the structure of a Rev dimer.
• Analysis of the crystal structure revealed protein-protein and protein-RNA interaction interfaces.
• The study focused on the structural arrangement of Rev oligomers.

Main Results:

• The crystal structure of a Rev dimer was solved at 2.5-Å resolution.
• The dimer structure shows arginine-rich helices positioned for binding adjacent RNA sites, coupling dimerization to RNA recognition.
• A second interface mediates higher-order oligomer formation, creating an adaptor for Crm1 binding.

Conclusions:

• Rev protein oligomerization is crucial for cooperative RRE binding and specificity.
• The oligomeric structure acts as an adaptor, presenting viral RNA and Crm1 to facilitate nuclear export.
• These findings provide insights into the mechanism of HIV RNA export and potential therapeutic targets.