Crosslinking network of a purified recombinant protein complex containing the human Cullin4-RING E3 ubiquitin ligase (CUL4A, ROC1, DDB1, DCAF1), hijacked by the retroviral protein Vpr and bound to the antiviral restriction factor SAMHD1. The network reports self-crosslinks (within an individual protein) and heteromeric crosslinks (between different protein complex subunits) from a Sulfo-SDA crosslinking data set, reported at <1% FDR on link level. The heteromeric crosslinks were analysed in Banchenko, Sofia et al, PLoS pathogens 2021, Fig. 5, and informed interpretation of low-resolution cryo-EM maps. This enabled us to decipher the mechanism how the retroviral accessory protein Vpr recruits the antiviral host factor SAMHD1 to the Cullin4-RING ligase, leading to SAMHD1 ubiquitylation and proteasomal degradation, and ultimately to improved virus replication conditions. The data have been deposited in PRIDE with the identifier PXD020453.