ArticlePloS one2009
An unusual helix turn helix motif in the catalytic core of HIV-1 integrase binds viral DNA and LEDGF.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- The HIV-1 integrase α4-helix involved in LTR-DNA recognition is also a highly antigenic peptide element.PloS one · 2010Article
- HIV-1 integrase and virus and cell DNAs: complex formation and perturbation by inhibitors of integration.Neurochemical research · 2010Article
- Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase.Virology journal · 2010Article
- Specificity of LTR DNA recognition by a peptide mimicking the HIV-1 integrase {alpha}4 helix.Nucleic acids research · 2009Article
- Piecing together the structure of retroviral integrase, an important target in AIDS therapy.The FEBS journal · 2009Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIntegrase (IN) of the type 1 human immunodeficiency virus (HIV-1) catalyzes the integration of viral DNA into host cellular DNA. We identified a bi-helix motif (residues 149-186) in the crystal structure of the catalytic core (CC) of the IN-Phe185Lys variant that consists of the alpha(4) and alpha(5) helices connected by a 3 to 5-residue turn. The motif is embedded in a large array of interactions that stabilize the monomer and the dimer. PRINCIPAL
findingsWe describe the conformational and binding properties of the corresponding synthetic peptide. This displays features of the protein motif structure thanks to the mutual intramolecular interactions of the alpha(4) and alpha(5) helices that maintain the fold. The main properties are the binding to: 1- the processing-attachment site at the LTR (long terminal repeat) ends of virus DNA with a K(d) (dissociation constant) in the sub-micromolar range; 2- the whole IN enzyme; and 3- the IN binding domain (IBD) but not the IBD-Asp366Asn variant of LEDGF (lens epidermal derived growth factor) lacking the essential Asp366 residue. In our motif, in contrast to the conventional HTH (helix-turn-helix), it is the N terminal helix (alpha(4)) which has the role of DNA recognition helix, while the C terminal helix (alpha(5)) would rather contribute to the motif stabilization by interactions with the alpha(4) helix.
conclusionThe motif, termed HTHi (i, for inverted) emerges as a central piece of the IN structure and function. It could therefore represent an attractive target in the search for inhibitors working at the DNA-IN, IN-IN and IN-LEDGF interfaces.
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