کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2184329 1095830 2015 17 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The Role of Packaging Sites in Efficient and Specific Virus Assembly
ترجمه فارسی عنوان
نقش سایت های بسته بندی در مجمع موثر و اختصاصی ویروس
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
چکیده انگلیسی


• During the life cycle of many viruses, a protein capsid must selectively assemble around the genomic RNA.
• RNA encapsidation is driven by nonspecific electrostatics and protein interactions with specific RNA sequences known as packaging sites.
• We use dynamical computer simulations to study how the selectivity conferred by packaging sites depends on solution conditions, protein interactions, and other control parameters.
• The simulations demonstrate that packaging sites enable extreme specificity, but only in certain regions of parameter space.
• Assembly around cognate (with packaging sites) and non-cognate (no packaging sites) RNAs can proceed by different classes of pathways.
• Understanding how nonspecific and specific interactions contribute to the efficiency and selectivity of assembly may promote efforts to develop antiviral agents that interfere with selective encapsidation of viral genomes.

During the life cycle of many single-stranded RNA viruses, including many human pathogens, a protein shell called the capsid spontaneously assembles around the viral genome. Understanding the mechanisms by which capsid proteins selectively assemble around the viral RNA amidst diverse host RNAs is a key question in virology. In one proposed mechanism, short sequences (packaging sites) within the genomic RNA promote rapid and efficient assembly through specific interactions with the capsid proteins. In this work, we develop a coarse-grained particle-based computational model for capsid proteins and RNA that represents protein–RNA interactions arising both from nonspecific electrostatics and from specific packaging site interactions. Using Brownian dynamics simulations, we explore how the efficiency and specificity of assembly depend on solution conditions (which control protein–protein and nonspecific protein–RNA interactions) and the strength and number of packaging sites. We identify distinct regions in parameter space in which packaging sites lead to highly specific assembly via different mechanisms and others in which packaging sites lead to kinetic traps. We relate these computational predictions to in vitro assays for specificity in which cognate viral RNAs compete against non-cognate RNAs for assembly by capsid proteins.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 427, Issue 15, 31 July 2015, Pages 2451–2467
نویسندگان
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