L368F/V408F double mutant of IBD of LEDGF/p75 retains interaction with M178I mutant of HIV-1 integrase

George, A and Raghavendra, N K (2017) L368F/V408F double mutant of IBD of LEDGF/p75 retains interaction with M178I mutant of HIV-1 integrase. Biochemical and Biophysical Research Communications, 490 (2). pp. 271-275. ISSN 0006-291X (In Press)

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Abstract

Lens-epithelium-derived-growth factor (LEDGF/p75) is an essential host protein for integration of HIV-1 DNA into host genome. Earlier alanine scanning mutational analysis has revealed that residues I365, D366 and F406 in the integrase binding domain (IBD) of p75 are critical for interaction with HIV-1 integrase (IN), while K364, V408 have intermediate effect and residues N367, L368, R405, K407 show wild type binding with IN. To gain insight into contribution of side chains of L368 and V408 that are adjacent to critical residues I365 and F406, respectively, site directed mutation of these residues to Ile/Leu, Met and Phe has been performed and characterized in this study. In contrast to alanine substitution, L368F mutation showed a ∼25% decrease, while V408L and V408F showed wild type binding, to IN. Docking analysis of I365, D366 and F406 mutants of IBD with IN predicts that interaction between residue M178(IN) and I365(IBD) might lead to an encounter complex formation. Accordingly, M178I mutant of IN failed to interact with IBD. Interestingly, a L368F/V408F double mutant of IBD restored binding to M178I mutant of IN, indicating that altered hydrophobicity in the inter helical loops of IBD might make I365 more accessible for interaction with IN.

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IITH Creators:
IITH CreatorsORCiD
Raghavendra, N Khttp://orcid.org/0000-0003-2220-1148
Item Type: Article
Uncontrolled Keywords: HIV; Integrase; LEDGF/p75; Inter helical loops; M178; L368
Subjects: Others > Biotechnology
Divisions: Department of Biotechnology
Depositing User: Team Library
Date Deposited: 19 Jun 2017 07:13
Last Modified: 14 Jan 2019 09:57
URI: http://raiith.iith.ac.in/id/eprint/3255
Publisher URL: https://doi.org/10.1016/j.bbrc.2017.06.035
OA policy: http://www.sherpa.ac.uk/romeo/issn/0006-291X/
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