Cellular Cofactors of Lentiviral Integrase: From Target Validation to Drug Discovery
Figure 1
Domain organization of HIV-1 IN and LEDGF/p75. (a) HIV-1 IN is composed of an N-terminal domain (NTD), a catalytic core domain (CCD), and a C-terminal domain (CTD). The CCD contains the catalytically essential DD(35)E motif and the hot spots for interaction with the IBD in LEDGF/p75. The Asp and Glu residues of the CCD coordinate one or two Mg2+ ions and are involved in 3′ processing and DNA strand-transfer activities. (b) LEDGF/p75 has several structural motifs involved in chromatin tethering and protein-protein interactions. The PWWP domain, the charged regions (CRs), and AT-hooks are involved in chromatin binding. The C-terminus contains the well-characterized IN binding domain (IBD) and acts as a protein interaction playground. Asp residue 366 critical for HIV-1 IN binding is indicated.
