Syn-2 PDZ1 substitutes for NC functionally and promotes ALIX-mediated HIV-1 budding. (A) Drawing of HIV-1 constructs used in this experiment and their ability to bind ALIX. ALIX engages in dual binding with WT HIV-1 NC and p6 domains, can stimulate the release of the PTAP- mutant. HIV-1 PDZ1 chimera where NC was replaced with Syn-2 PDZ1 is shown (B) Syn-2 PDZ1 substitutes for NC functionally. 293T cells were transfected with either HIV-1 PTAP- (lane 1) or with HA-ALIX (lane 2), with HIV-1 PTAP-PDZ1 chimera alone (lane 3), with increasing amounts of HA-ALIX (lanes 4 and 5) or HA-Nedd4-2s (lane 6). Cells, virus and input were analyzed by SDS-PAGE and WB as indicated. Inset shows the WB of higher amounts of virus released (lanes 3–5). (C) Gag-PDZ1 requires access to membrane- and ESCRT-binding ALIX Bro1 to promote HIV-1 budding. Experiments identical to those described in B were performed with the addition of ALIX I212D and ALIX105 (lanes 5, 6).