Fig. 1

A model of HIV-1 nuclear import. Nuclear import of the HIV-1 PIC is driven by the cellular proteins karyopherin α and karyopherin β. Two MA NLSs (NLS1 and NLS2) provide the connection between the PIC and karyopherin α. NLS 1 (amino acids 26–32) is a stronger NLS than NLS2 (amino acids 109–113), but they may cooperate to form a bipartite NLS, thus interacting with the same region on karyopherin α. Alternatively, they may bind to adjacent NLS-binding sites on karyopherin α. The role of Vpr is to strengthen interaction between the MA NLSs and karyopherin α. This is likely achieved by a conformational change in the karyopherin-α molecule upon binding of Vpr. This binding involves a site different from the NLS-binding site on α. The import complex is then targeted to the nuclear pore via interaction between karyopherin β and xxFG-repeat-containing nucleoporins. Other details are in the text.