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Isoform-specific determinants in the HP1 binding to histone 3: insights from molecular simulations.

Abstract : Despite the significant improvements in anti HIV-1 treatment, AIDS remains a lifelong disease due to the impossibility to eradicate the viral reservoir established upon integration of the viral genome. Controlling the epigenetic block imposed by the host cell machinery to the viral transcription may represent a therapeutic alternative to purge the viral reservoir, offering a way to eradicate the infection. Heterochromatin protein 1 (HP1) has been reported to actively participate in the silencing of HIV-1 integrated genome by binding to histone 3 (H3) tail. This interaction is mediated by the Chromodomain of HP1. Nevertheless, the structural features that determine its binding to H3 tail upon post-transductional modifications, such as methylation and phosphorylation as well as isoform-specific effects have not yet been described. We have undertaken the systematic simulation of the Chromodomains of the isoforms beta and gamma of HP1 in complex with the H3 tail methylated at Lys9 in presence/absence of phosphorylation at Ser10. Our results pinpoint isoform-specific electrostatic interactions as important determinants for the stability of the complexes. Characterization of intermolecular contacts between HP1 variants and H3 furnishes new insights on isoform-specific recognition and the effect of phosphorylation.
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Submitted on : Friday, March 30, 2012 - 9:55:32 PM
Last modification on : Thursday, August 8, 2019 - 9:32:01 AM

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Matias R Machado, Pablo D Dans, Sergio Pantano. Isoform-specific determinants in the HP1 binding to histone 3: insights from molecular simulations.. Amino Acids, Springer Verlag, 2010, 38 (5), pp.1571-81. ⟨10.1007/s00726-009-0371-3⟩. ⟨pasteur-00684218⟩



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