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Báo cáo y học: " Analysis of the PDZ binding specificities of Influenza A Virus NS1 proteins"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Analysis of the PDZ binding specificities of Influenza A Virus NS1 proteins | Thomas et al. Virology Journal 2011 8 25 http www.virologyj.eom content 8 1 25 J VIROLOGY JOURNAL RESEARCH Open Access Analysis of the PDZ binding specificities of Influenza A Virus NS1 proteins 1 1 13 24 1 Miranda Thomas Christian Kranjec Kazunori Nagasaka Greg Matlashewski Lawrence Banks Abstract The Influenza A virus non-structural protein 1 NS1 is a multifunctional virulence factor with several protein-protein interaction domains involved in preventing apoptosis of the infected cell and in evading the interferon response. In addition the majority of influenza A virus NS1 proteins have a class I PDZ-binding motif at the C-terminus and this itself has been shown to be a virulence determinant. In the majority of human influenza NS1 proteins the consensus motif is RSxV in avian NS1 it is ESxV. Of the few human strains that have the avian motif all were from very high mortality outbreaks of the disease. Previous work has shown that minor differences in PDZ-binding motifs can have major effects on the spectrum of cellular proteins targeted. In this study we analyse the effect of these differences upon the binding of Influenza A virus NS1 protein to a range of cellular proteins involved in polarity and signal transduction. Introduction The Influenza A virus NS1 protein non-structural protein 1 is extremely important in the pathology of the virus. It is not a virion component but is expressed early in infection. It is a multifunctional virulence factor and many of its effects are modulated by activation of PI3K which it binds via its SH3 domain 1-4 . The influenza A virus NS1 protein has several protein interaction sites including SH2 and SH3 domains as well as recognition sites for kinases including CK2 and MAPK. In addition over 99 of NS1 proteins isolated have a class 1 PDZ binding motif PBM at the C-terminus 5 . PDZ domains are 80-90 amino acid domains that function as docking regions for protein-protein interactions 6 7 and PDZ-containing proteins were originally