Biomaterial Database

Transcriptional coactivator LEDGF/p75 modulates human immunodeficiency virus type 1 integrase-mediated concerted integration. 2007

Krishan K Pandey, and Sapna Sinha, and Duane P Grandgenett

Institute for Molecular Virology, 3681 Park Avenue, Saint Louis University Health Sciences Center, St. Louis, MO 63110, USA. pandeykk@slu.edu

Human transcriptional coactivator p75/lens epithelium-derived growth factor (LEDGF) binds human immunodeficiency virus type 1 (HIV-1) integrase (IN). We studied the effects of LEDGF on the assembly and activity of HIV-1 synaptic complexes, which, upon association with a target, mediate concerted integration of viral DNA substrates in vitro. We found that while augmenting single-ended viral DNA integration into target DNA, the host factor was able to either stimulate or abrogate concerted integration in a concentration-dependent manner. LEDGF modestly stimulated (two- to threefold) concerted integration at low molar ratios to IN (<1). The modest stimulation was independent of solution conditions and several different viral DNA substrates. In solution, concerted integration was inhibited if the molar ratios of LEDGF to IN were >1, apparently due to the disruption of IN-IN interactions essential for the formation of active synaptic complexes prior to their association with a circular target. The isolated IN binding domain of LEDGF was sufficient to stimulate and inhibit concerted integration, as observed with full-length protein, albeit at lower efficiencies. Our data show that LEDGF differentially affects IN-DNA complexes mediating single-ended viral DNA integration and synaptic complexes mediating concerted integration. Synaptic complexes associated with target, termed strand transfer complexes, are resistant to disruption by high concentrations of LEDGF. The results suggest that LEDGF may influence HIV-1 integration in vivo.

UI	MeSH Term	Description	Entries
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011995	Recombination, Genetic	Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.	Genetic Recombination,Recombination,Genetic Recombinations,Recombinations,Recombinations, Genetic
D004279	DNA, Viral	Deoxyribonucleic acid that makes up the genetic material of viruses.	Viral DNA
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014157	Transcription Factors	Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.	Transcription Factor,Factor, Transcription,Factors, Transcription
D015497	HIV-1	The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.	Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D016662	Virus Integration	Insertion of viral DNA into host-cell DNA. This includes integration of phage DNA into bacterial DNA; (LYSOGENY); to form a PROPHAGE or integration of retroviral DNA into cellular DNA to form a PROVIRUS.	Integration, Provirus,Integration, Virus,Provirus Integration,Viral integration,Integrations, Provirus,Integrations, Virus,Provirus Integrations,Viral integrations,Virus Integrations,integration, Viral,integrations, Viral
D017434	Protein Structure, Tertiary	The level of protein structure in which combinations of secondary protein structures (ALPHA HELICES; BETA SHEETS; loop regions, and AMINO ACID MOTIFS) pack together to form folded shapes. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure.	Tertiary Protein Structure,Protein Structures, Tertiary,Tertiary Protein Structures
D048868	Adaptor Proteins, Signal Transducing	A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes	Signal Transducing Adaptor Proteins