Molecular determinants for recognition of divergent SAMHD1 proteins by the lentiviral accessory protein Vpx.
Bottom Line: Comparison with Vpx from SIV that infects sooty mangabeys (SIVsmm) complexed with SAMHD1-DCAF1 identifies molecular determinants directing Vpx lineages to N- or C-terminal SAMHD1 sequences.Inspection of the Vpx-DCAF1 interface also reveals conservation of Vpx with the evolutionally related HIV-1/SIV accessory protein Vpr.These data suggest a unified model for how Vpx and Vpr exploit DCAF1 to promote viral replication.
Affiliation: Division of Molecular Structure, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.Show MeSH
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Mentions: To gain further insights into molecular recognition in the SIVmnd-2 Vpx system, SIVmnd-2 Vpx, SAMHD1mnd-NtD, and DCAF1-CtD (Figure 2A) were assembled in vitro using recombinant proteins and the ternary complex purified by size-exclusion chromatography (Figure 2B). The protein complex crystallized in space group P6522, the crystals diffracted to 2.8 Å resolution, and the structure was solved by molecular replacement using the SIVsmm Vpx/SAMHD1hs-CtD/DCAF1-CtD structure (Schwefel et al., 2014) as a search model. Details of the data collection, structure determination, map quality, and refinement are presented in Table 1 and Figure S2.
Affiliation: Division of Molecular Structure, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.