2B4J: Structural Basis For The Recognition Between Hiv-1 Integrase And Ledgf/p75

Integrase (IN) is an essential retroviral enzyme, and human transcriptional coactivator p75, which is also referred to as lens epithelium-derived growth factor (LEDGF), is the dominant cellular binding partner of HIV-1 IN. Here, we report the crystal structure of the dimeric catalytic core domain of HIV-1 IN complexed to the IN-binding domain of LEDGF. Previously identified LEDGF hotspot residues anchor the protein to both monomers at the IN dimer interface. The principal structural features of IN that are recognized by the host factor are the backbone conformation of residues 168-171 from one monomer and a hydrophobic patch that is primarily comprised of alpha-helices 1 and 3 of the second IN monomer. Inspection of diverse retroviral primary and secondary sequence elements helps to explain the apparent lentiviral tropism of the LEDGF-IN interaction. Because the lethal phenotypes of HIV-1 mutant viruses unable to interact with LEDGF indicate that IN function is highly sensitive to perturbations of the structure around the LEDGF-binding site, we propose that small molecule inhibitors of the protein-protein interaction might similarly disrupt HIV-1 replication.
PDB ID: 2B4JDownload
MMDB ID: 35690
PDB Deposition Date: 2005/9/24
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.02  Å
Source Organism:
Human immunodeficiency virus 1
Similar Structures:
Biological Unit for 2B4J: tetrameric; determined by author and by software (PISA)
Molecular Components in 2B4J
Label Count Molecule
Proteins (4 molecules)
Integrase (In)
Molecule annotation
PC4 and Sfrs1 Interacting Protein(Gene symbol: PSIP1)
Molecule annotation
Chemicals (6 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB