tailieunhanh - Báo cáo y học: " Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human "

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Retrovirology cung cấp cho các bạn kiến thức về ngành y đề tài: " Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human. | Huang et al. Retrovirology 2010 7 24 http content 7 1 24 RETR0VIR0L0GY RESEARCH Open Access Cysteine 95 and other residues influence the regulatory effects of Histidine 69 mutations on Human Immunodeficiency Virus Type 1 protease autoprocessing Liangqun Huang Alyssa Hall Chaoping Chen Abstract Background Regulated autoprocessing of HIV Gag-Pol precursor is required for the production of mature and fully active protease. We previously reported that H69E mutation in a pseudo wild type protease sequence significantly 20-fold impedes protease maturation in an in vitro autoprocessing assay and in transfected mammalian cells. Results Interestingly H69E mutation in the context of a laboratory adapted NL4-3 protease showed only moderate inhibition 4-fold on protease maturation. There are six point mutations Q7K L33I N37S L63I C67A and C95A between the NL4-3 and the pseudo wild type proteases suggesting that the H69E effect is influenced by other residues. Mutagenesis analyses identified C95 as the primary determinant that dampened the inhibitory effect of H69E. L63 and C67 also demonstrated rescue effect to a less extent. However the rescue was completely abolished when H69 was replaced by aspartic acid in the NL4-3 backbone. Charge substitutions of surface residues E21 D30 E34 E35 and F99 to neutral or positively charged amino acids failed to restore protease autoprocessing in the context of H69E mutation. Conclusions Taken together we suggest that residue 69 along with other amino acids such as C95 plus L63 and C67 to a less extent modulate precursor structures for the regulation of protease autoprocessing in the infected cell. Background Human immunodeficiency virus 1 HIV-1 is a member of the lentivirus genus in the retroviradae superfamily. In the HIV infected cell the unspliced genomic RNA also serves as mRNA for translation of two polyproteins Gag and Gag-Pol 1 2 . Gag polyprotein is the primary viral determinant responsible for the assembly and

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