Structural basis of diverse substrate recruitment by the HIV-1 Vpr-hijacked CRL4(VprBP) E3 ligase.

Vpr hijacks the CRL4(VprBP) E3 ligase by utilizing flexible ARM-like domains to recruit diverse substrates, enabling targeted degradation of host restriction factors.

• Why it matters: Understanding how HIV-1 Vpr recruits various substrates to the host's degradation machinery is crucial for developing targeted therapies against viral manipulation of cellular processes.
• What they did: The study analyzed the molecular architecture of the DDB1-VprBP complex and its interaction with different Vpr-substrates using structural characterization, revealing conformational flexibility in ARM-like domains.
• The result: Findings show that ARM-like domains switch between "up" and "down" conformations to accommodate substrates of different sizes, providing insights for designing targeted protein degradation strategies.