Figure 3
From: MxB binds to the HIV-1 core and prevents the uncoating process of HIV-1
The interaction of MxB with the HIV-core is inhibited by a small-molecule that binds into a pocket between the bases of the Cyp A binding loop and the loop that connects helices 6 and 7 of HIV-1 capsid. (A) The ability of MxB-FLAG (upper left panel), CPSF6-FLAG (upper right panel), TRIM5αrh-HA (lower left panel), and TRIMCyp-HA (lower right panel) to bind in vitro assembled HIV-1 CA-NC complexes was measured in the presence of the indicated concentration of the small molecules PF74, BI-2, CPIPB (4-{2-[3-(3-clorophenyl)-1H-pyrazol-4-yl]-1-[3-(1H-imidazol-1-yl-propyl]-1H-benzimidazol-5-yl} benzoic acid), CAP-1 and the peptide CAI, as described in Methods. Similar results were obtained in three independent experiments and a representative experiment is shown. (B) The ability of MxB to bind in vitro assembled HIV-1 CA-NC complexes in the presence of the indicated concentrations of the small molecule CPIPB (upper left panel), BI-2 (upper right panel), CAP-1 (bottom left panel) and PF74 (bottom right panel) was measured. Similar results were obtained in three independent experiments and a representative experiment is shown. (C) Chemical structure of the small molecule CPIPB is shown (left panel). Surface representation of the X-ray structure of the HIV-1 capsid in complex with CPIPB (PDB entry 4E91) (middle panel). Surface representation of the X-ray structure of the HIV-1 CA hexamer (PDB entry 3H4E) showing in orange residues that directly interact with CPIPB on the surface of the HIV-1 capsid.