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: A structural constraint for functional interaction between N-terminal and C-terminal domains in simian immunodeficiency virus capsid proteins. | Inagaki et al. Retrovirology 2010 7 90 http content 7 1 90 RETR0VIR0L0GY RESEARCH Open Access A structural constraint for functional interaction between N-terminal and C-terminal domains in simian immunodeficiency virus capsid proteins 1 1 2 2 3 1 Natsuko Inagaki Hiroaki Takeuchi Masaru Yokoyama Hironori Sato Akihide Ryo Hiroyuki Yamamoto Miki Kawada1 Tetsuro Matano1 Abstract Background The Gag capsid CA is one of the most conserved proteins in highly-diversified human and simian immunodeficiency viruses HIV and SIV . Understanding the limitations imposed on amino acid sequences in CA could provide valuable information for vaccine immunogen design or anti-HIV drug development. Here by comparing two pathogenic SIV strains SIVmac239 and SIVsmE543-3 we found critical amino acid residues for functional interaction between the N-terminal and the C-terminal domains in CA. Results We first examined the impact of Gag residue 205 aspartate Gag205D in SIVmac239 and glutamate Gag205E in SIVsmE543-3 on viral replication due to this difference Gag206-216 IINEEAADWDL epitope-specific cytotoxic T lymphocytes CTLs were previously shown to respond to SIVmac239 but not SIVsmE543-3 infection. A mutant SIVmac239 SIVmac239Gag205E whose Gag205D is replaced with Gag205E showed lower replicative ability. Interestingly however SIVmac239Gag205E passaged in macaque T cell culture often resulted in selection of an additional mutation at Gag residue 340 a change from SIVmac239 valine Gag340V to SIVsmE543-3 methionine Gag340M with recovery of viral fitness. Structural modeling analysis suggested possible intermolecular interaction between the Gag205 residue in the N-terminal domain and Gag340 in the C-terminal in CA hexamers. The Gag205D-to-Gag205E substitution in SIVmac239 resulted in loss of in vitro core stability which was recovered by additional Gag340V-to-Gag340M substitution. Finally selection of Gag205E plus Gag340M mutations but not Gag205E alone was observed in a
