کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2828463 1162709 2015 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Characterization of the termini of the West Nile virus genome and their interactions with the small isoform of the 2′ 5′-oligoadenylate synthetase family
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Characterization of the termini of the West Nile virus genome and their interactions with the small isoform of the 2′ 5′-oligoadenylate synthetase family
چکیده انگلیسی

2′ 5′-Oligoadenylate synthetases (OAS) are interferon-stimulated proteins that act in the innate immune response to viral infection. Upon binding viral double-stranded RNA, OAS enzymes produce 2′-5′-linked oligoadenylates that stimulate RNase L and ultimately slow viral propagation. Truncations/mutations in the smallest human OAS isoform, OAS1, results in susceptibility to West Nile virus (WNV). We have previously demonstrated in vitro the interaction between OAS1 and the 5′-terminal region of the WNV RNA genome. Here we report that the 3′-terminal region is also able to mediate specific interaction with and activation of OAS1. Binding and kinetic experiments identified a specific stem loop within the 3′-terminal region that is sufficient for activation of the enzyme. The solution conformation of the 3′-terminal region was determined by small angle X-ray scattering, and computational models suggest a conformationally restrained structure comprised of a helix and short stem loop. Structural investigation of the 3′-terminal region in complex with OAS1 is also presented. Finally, we show that genome cyclization by base pairing between the 5′- and 3′-terminal regions, a required step for replication, is not sufficient to protect WNV from OAS1 recognition in vitro. These data provide a physical framework for understanding recognition of the highly structured terminal regions of a flaviviral genome by an innate immune enzyme.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Structural Biology - Volume 190, Issue 2, May 2015, Pages 236–249
نویسندگان
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