. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . "LEDGF/p75 complexes with HIV-1 integrase and stimulates integrase strand transfer activity in vitro" . "The interaction of HIV-1 integrase with LEDGF/p75 accounts for the karyophilic properties and chromosomal targeting of integrase, which co-localizes with LEDGF/p75 in the nuclei of human cells" . "The N-terminal zinc binding domain (amino acids 1-52) and the central core domain (amino acids 53-212) of HIV-1 integrase are involved in the interaction with LEDGF/p75, with the core domain harboring the main determinant for interaction" . "The 146-156 amino acid stretch of LEDGF/p75 is critical for nuclear localization and a single amino acid mutation at K150A in LEDGF/p75 renders HIV-1 integrase cytoplasmic" . "In LEDGF/p75 knock-down cells, there is an increase in ubiquitinated HIV-1 integrase, which is found exclusively in the cytoplasm of these cells, and protection of HIV-1 integrase from the proteasome requires only interaction with LEDGF/p75" . "Using a pull-down assay, LEDGF/p75 interacts with HIV-1, HIV-2, and FIV integrases and strongly promotes the binding of HIV-1 integrase to DNA in vitro" . "The NMR structure of the integrase-binding domain (IBD) in LEDGF/p75 reveals that residues Ile365, Asp366, or Phe406 in LEDGF/p75 mediate binding to HIV-1 integrase, and amino acids 165-173 of HIV-1 integrase are involved in the binding to LEDGF/p75" . "A single mutation at residue Q168 of HIV-1 integrase disrupts its interaction with LEDGF/p75 and results in defective HIV-1 replication" . "HIV-1 integration in cells depleted for LEDGF/p75 is less frequent in transcription units, less frequent in genes regulated by LEDGF/p75 and more frequent in GC-rich DNA" . "LEDGF/p75 binds to HIV-1 integrase (IN) and tethers IN to chromatin; the N-terminal PWWP domain (residues 1-93) in LEDGF/p75, and its beta-barrel substructure (first 63 residues) are required for chromatin binding and IN tethering to chromatin" . "A single mutation at residue A128 or H171 of HIV-1 integrase diminishes its interaction with LEDGF/p75" . "Intensified RNA interference and dominant-negative protein approaches show that LEDGF/p75 is an essential linkage between HIV-1 integrase and chromatin" . "Overexpression of the integrase binding domain (IBD) of LEDGF/p75 severely inhibits HIV-1 replication, while no inhibition is observed in cell lines overexpressing the interaction-deficient D366A mutant of integrase" . "LEDGF/p75 interferes with HIV-1 integrase (IN) full-site product formation by competing for HIV-1 IN dimer-dimer interactions or interfering with assembled synaptic complexes that harbor a single integrated end" . "Studies on integrase strand transfer activity in vitro show that LEDGF/p75 only binds HIV-1 integrase before the latter binds donor DNA, whereas donor DNA engages either free or LEDGF/p75-bound integrase" . "T-cell lines expressing a C-terminal fragment (residues 325-530) of LEDGF/p75 exhibit a reduced affinity of integrase for LEDGF/p75 and the blockage of viral replication. Both A128T and E170G IN mutations are together sufficient for viral rescue" . "LEDGF-derived peptides inhibit HIV-1 IN binding to DNA by shifting its oligomerization equilibrium toward the tetramer. The LEDGF peptides inhibit HIV-1 replication in cell culture by eliminating viral DNA integration" . "HIV-1 integrase (IN) and JPO2 bind mutually exclusively to LEDGF/p75. Two LEDGF/p75 mutants (I365A and D366N) abrogate interaction between LEDGF/p75 and IN but interact with JPO2 to the same extent as wild-type LEDGF/p75" . "Results from molecular dynamics simulations show residues Gln168, Glu170 and Thr174 in chain A of HIV-1 Integrase (IN), Thr125 and Trp131 in chain B of IN as well as Ile365, Asp366, Phe406 and Val408 in LEDGF/p75 are responsible for IN-LEDGF/p75 binding" . "LEDGF strongly stabilizes HIV-1 integrase-LEDGF/p75 interactions and promotes IN tetramerization" . "HIV-1 IN mutants (V165A, A179P, and KR186,7AA) exhibit no chromatin-binding ability and fails to interact with LEDGF/p75" . "A bi-helix motif (residues 149-186) in HIV-1 IN consists of the alpha(4) and alpha(5) helices connected by a 3 to 5-residue turn and binds to the LTR ends of virus DNA and to the IN binding domain (IBD) but not the IBD-Asp366Asn variant of LEDGF" . "Two LEDGF mutants (K401E/K402S/R405E and K401E/K402E/R405E) fail to interact with HIV-1 IN. The IN mutant (D6K/E10K/E13K) complements the interaction with the LEDGF mutant (K401E/K402E/R405E)" . "Mass spectrometry analysis shows a stable complex between human LEDGF/p75 and HIV-1 IN with a stoichiometry of 2 LEDGF/p75 and 4 IN" . "A domesticated transposase, pogZ, carries a DDE domain (amino acids 1117-1323) and interacts with LEDGF/p75. HIV-1 IN is efficient in displacing pogZ from LEDGF/p75" . "Replacing the N-terminal domain ensemble (NDE) of IN with strongly divergent chromatin-binding modules (i.e. H1 or KSHV LANA) can rescue integrase tethering and HIV-1 integration in LEDGF/p75-deficient cells" . "Three peptides (354-378, 360-370, 400-413) derived from the IBD of LEDGF compete with LEDGF binding to HIV-1 IN. LEDGF-354-378 peptide shows the strongest binding competition" . "HIV-1 Rev interacts with LEDGF/p75 to promote dissociation of HIV-1 IN-LEDGF/p75 complex" . "A serine cluster (residues 271, 273, and 275) in LEDGF/p75 is phosphorylated by protein kinase casein kinase 2 (PKCK2). S271/273/275A mutant impairs LEDGF/p75-mediate HIV-1 DNA integration without altering IN and chromatin binding" . "Alanine scan, fluorescence anisotropy studies, homology modeling and NMR demonstrate that all residues in LEDGF 361-370 contribute to IN binding and inhibition. Kinetic studies in cells show direct inhibition of viral cDNA integration by LEDGF 361-370" . "HIV-1 IN mutants (H171A, L172A, and EH170,1AA), located between the alpha4 and alpha5 helices of IN, severely impair the interaction with LEDGF/p75 but are still able to bind chromatin, suggesting IN-mediated LEDGF-independent chromatin targeting" . "The C-terminal domain of HIV-1 IN is masked in the presence of LEDGF/p75 protein in cell lysates, suggesting a structural rearrangement or oligomerization of IN" . "Analytical ultracentrifugation indicates IN (amino acids 1-212) and LEDGF/p75 (amino acids 347-471) form a complex with a molecular weight consistent with a 2:2 complex" . "Multiangle light scattering and small angle x-ray scattering analysis indicate full-length IN (C56S/F139D/F185H/C280S) and LEDGF/p75 (amino acids 347-471) form a tetramer, where each IN dimer binds only one LEDGF/p75" . "Multiangle light scattering and small angle x-ray scattering analysis indicate full-length IN (wild-type and C56S/F139D/F185H/C280S mutant) and LEDGF/p75 (amino acids 325-530) form a tetramer complex with stoichiometry 4:4" . "2-(quinolin-3-yl) acetic acid derivatives inhibit the IN-LEDGF interaction in vitro and impair HIV-1 replication in infected cells." . "HIV-1 integrase (IN) increases the binding strength of LEDGF/p75 deltaPWWP to chromatin, which requires the direct interaction of these two proteins. Integrase fails to increase chromatin binding of a LEDGF/p75 deltaPWWP/AT mutant" . "The NLS (amino acids 148-156) and AT-hook like domains (amino acids 178-197) constitute important contributions to enhance the binding of HIV-1 Integrase (IN) to DNA" . "N-(cyclohexylmethyl)-2,3-dihydroxy-5-(piperidin-1-ylsulfonyl) benzamide (5u) inhibits the HIV-1 IN-LEDGF/p75 interaction" . "HIV-1 IN mutant K264E supports the wild-type level of concerted integration activity and the efficient integration of endogenous viral DNA in vitro in the presence of LEDGF/p75" . "Small molecules, tert-Butoxy-(4-phenyl-quinolin-3-yl)-acetic acids (tBPQA), are identified to inhibit HIV-1 IN dimerization, IN/viral DNA assembly, and/or IN/LEDGF interaction" . "The triple mutant RRK262/3/4/EEE in HIV-1 IN still maintains wild type levels of binding with LEDGF/p75" . "HIV-1 Pol is identified to have a physical interaction with PC4 and SFRS1 interacting protein 1 (PSIP1; p75/LEDGF) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses" . "Affinity Capture-Western; Co-crystal Structure; Reconstituted Complex" . "BioGRID" . "interacts with" . "inhibited by" . "regulated by" . "co-localizes with" . "upregulates" . "binds" . "competes with" . "complexes with" . "stimulated by" . "stabilized by" . "imported by" .