<p>Cryo-EM data processing workflow of DDB1-VprBP.</p>

The viral accessory protein Vpr is the key protein that recruits diverse substrates to the receptor VprBP for proteasomal degradation. However, the underlying molecular mechanism remains poorly understood.

Here, we characterize the molecular architecture of the DDB1-VprBP substrate recognition unit alone and in complex with different Vpr-substrates. Our results pinpoint that the LisH domain of VprBP mediates the DDB1-VprBP dimerization. Of note, the Armadillo-like (ARM-like) domains of VprBP adopt either an “up” or “down” conformation that may assist in accommodating Vpr-substrates of divergent stoichiometries and sizes.