流感病毒的NS1蛋白是一個關(guān)鍵致病因子,，它通過多種機制,、包括雙鏈RNA的結(jié)合和隔離來拮抗宿主的抗病毒反應(yīng),。
在新一期Nature中,，美國貝勒醫(yī)學(xué)院的研究人員利用在2004年越南禽流感爆發(fā)期間分離出的一個惡性H5N1禽流感病毒毒株,，確定了全長NS1蛋白的結(jié)構(gòu),。該分子的RNA結(jié)合區(qū)域與非H5N1毒株的RNA結(jié)合區(qū)域相比有微妙的差別，而效應(yīng)子區(qū)域則有較大改變,。這兩個區(qū)域以某種方式發(fā)生相互作用,，形成小管，后者可能會隔離雙鏈RNA,，從而讓病毒躲過宿主的先天免疫反應(yīng),。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 456, 985-988 (18 December 2008) | doi:10.1038/nature07444
X-ray structure of NS1 from a highly pathogenic H5N1 influenza virus
Zachary A. Bornholdt1 & B. V. Venkataram Prasad1,2
1 Department of Molecular Virology and Microbiology,
2 Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
The recent emergence of highly pathogenic avian (H5N1) influenza viruses, their epizootic and panzootic nature, and their association with lethal human infections have raised significant global health concerns1, 2. Several studies have underlined the importance of non-structural protein NS1 in the increased pathogenicity and virulence of these strains3, 4. NS1, which consists of two domains—a double-stranded RNA (dsRNA) binding domain5, 6 and the effector domain7, separated through a linker—is an antagonist of antiviral type-I interferon response in the host8, 9. Here we report the X-ray structure of the full-length NS1 from an H5N1 strain (A/Vietnam/1203/2004) that was associated with 60% of human deaths in an outbreak in Vietnam1, 2. Compared to the individually determined structures of the RNA binding domain and the effector domain from non-H5N1 strains, the RNA binding domain within H5N1 NS1 exhibits modest structural changes, while the H5N1 effector domain shows significant alteration, particularly in the dimeric interface. Although both domains in the full-length NS1 individually participate in dimeric interactions, an unexpected finding is that these interactions result in the formation of a chain of NS1 molecules instead of distinct dimeric units. Three such chains in the crystal interact with one another extensively to form a tubular organization of similar dimensions to that observed in the cryo-electron microscopy images of NS1 in the presence of dsRNA. The tubular oligomeric organization of NS1, in which residues implicated in dsRNA binding face a 20-?-wide central tunnel, provides a plausible mechanism for how NS1 sequesters varying lengths of dsRNA, to counter cellular antiviral dsRNA response pathways, while simultaneously interacting with other cellular ligands during an infection.
