Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: HIV-1 integrase modulates the interaction of the HIV-1 cellular cofactor LEDGF/p75 with chromatin. | Astiazaran et al. Retrovirology 2011 8 27 http content 8 1 27 RETR0VIR0L0GY RESEARCH Open Access HIV-1 integrase modulates the interaction of the HIV-1 cellular cofactor LEDGF p75 with chromatin Paulina Astiazarant Murilo TD Bueno1 Elisa Morales 1 Jeffrey R Kugelman Jose A Garcia-Rivera and Manuel Llano Abstract Background Chromatin binding plays a central role in the molecular mechanism of LEDGF p75 in HIV-1 DNA integration. Conflicting results have been reported in regards to the relevance of the LEDGF p75 chromatin binding element PWWP domain in its HIV-1 cofactor activity. Results Here we present evidence that re-expression of a LEDGF p75 mutant lacking the PWWP domain APWWP rescued HIV-1 infection in cells verified to express background levels of endogenous LEDGF p75 that do not support efficient HIV-1 infection. The HIV-1 cofactor activity of LEDGF p75 APWWP was similar to that of LEDGF p75 wild type WT . A possible molecular explanation for the nonessential role of PWWP domain in the HIV-1 cofactor activity of LEDGF p75 comes from the fact that coexpression of HIV-1 integrase significantly restored the impaired chromatin binding activity of LEDGF p75 APWWP. However integrase failed to promote chromatin binding of a non-chromatin bound LEDGF p75 mutant that lacks both the PWWP domain and the AT hook motifs APWWP AT and that exhibits negligible HIV-1 cofactor activity. The effect of integrase on the chromatin binding of LEDGF p75 requires the direct interaction of these two proteins. An HIV-1 integrase mutant unable to interact with LEDGF p75 failed to enhance chromatin binding whereas integrase wild type did not increase the chromatin binding strength of a LEDGF p75 mutant lacking the integrase binding domain AIBD . Conclusions Our data reveal that the PWWP domain of LEDGF p75 is not essential for its HIV-1 cofactor activity possibly due to an integrase-mediated increase of the chromatin binding strength of this LEDGF p75 mutant. .