Subscribe to the gold package and get unlimited access to Shamra Academy
Register a new userQuasi-Equilibrium Self-Assembly of Small RNA Viruses
441
0
0.0
(
0
)
Ask ChatGPT about the research
No Arabic abstract
We propose a description for the quasi-equilibrium self-assembly of small, single-stranded (ss) RNA viruses whose capsid proteins (CPs) have flexible, positively charged, disordered tails that associate with the negatively charged RNA genome molecules. We describe the assembly of such viruses as the interplay between two coupled phase-transition like events: the formation of the protein shell (the capsid) by CPs and the condensation of a large ss viral RNA molecule. Electrostatic repulsion between the CPs competes with attractive hydrophobic interactions and attractive interaction between neutralized RNA segments mediated by the tail-groups. An assembly diagram is derived in terms of the strength of attractive interactions between CPs and between CPs and the RNA molecules. It is compared with the results of recent studies of viral assembly. We demonstrate that the conventional theory of self-assembly, which does describe the assembly of textit{empty} capsids, is in general not applicable to the self-assembly of RNA-encapsidating virions.
rate research
Read More
We present a simple kinetic model for the assembly of small single-stranded RNA viruses that can be used to carry out analytical packaging contests between different types of RNA molecules. The RNA selection mechanism is purely kinetic and based on small differences between the assembly energy profiles. RNA molecules that win these packaging contests are characterized by having a minimum Maximum Ladder Distance and a maximum Wrapping Number.The former is a topological invariant that measures the branchiness of the genome molecule while the latter measures the ability of the genome molecule to maximally associate with the capsid proteins. The model can also be used study the applicability of the theory of nucleation and growth to viral assembly, which breaks down with increasing strength of the RNA-protein interaction.
Single-stranded (ss) RNA viruses self-assemble spontaneously in solutions that contain the viral RNA genome molecules and the viral capsid proteins. The self-assembly of empty capsids can be understood on the basis of free energy minimization of rather simple models. However, during the self-assembly of complete viral particles in the cytoplasm of an infected cell, the viral genome molecules must be selected from a large pool of very similar host messenger RNA molecules. It is known that the assembly process takes the form of preferential heterogeneous nucleation of capsid proteins on viral RNA molecules (selective nucleation). Recently, a simple mathematical model was proposed for the selective nucleation of small ssRNA viruses. In this paper we present a statistical physics analysis of the thermal equilibrium and kinetic properties of that model and show that it can account, at least qualitatively, for numerous observations of the self-assembly of small ssRNA viruses.
The formation of a viral capsid -- the highly-ordered protein shell that surrounds the genome of a virus -- is the canonical example of self-assembly. The capsids of many positive-sense RNA viruses spontaneously assemble from in vitro mixtures of the coat protein and RNA. The high yield of proper capsids that assemble is remarkable, given their structural complexity: 180 identical proteins must arrange into three distinct local configurations to form an icosahedral capsid with a triangulation number of 3 (T = 3). Despite a wealth of data from structural studies and simulations, even the most fundamental questions about how these structures assemble remain unresolved. Experiments have not determined whether the assembly pathway involves aggregation or nucleation, or how the RNA controls the process. Here we use interferometric scattering microscopy to directly observe the in vitro assembly kinetics of individual, unlabeled capsids of bacteriophage MS2. By measuring how many coat proteins bind to individual MS2 RNA strands over time scales from 1 ms to 900 s, we find that the start of assembly is broadly distributed in time and is followed by a rapid increase in the number of bound proteins. These measurements provide strong evidence for a nucleation-and-growth pathway. We also find that malformed structures assemble when multiple nuclei appear on the same RNA before the first nucleus has finished growing. Our measurements reveal the complex assembly pathways for viral capsids around RNA in quantitative detail, including the nucleation threshold, nucleation time, growth time, and constraints on the critical nucleus size. These results may inform strategies for engineering synthetic capsids or for derailing the assembly of pathogenic viruses.
Understanding the interactions between viruses and surfaces or interfaces is important, as they provide the principles underpinning the cleaning and disinfection of contaminated surfaces. Yet, the physics of such interactions is currently poorly understood. For instance, there are longstanding experimental observations suggesting that the presence of air-water interfaces can generically inactivate and kill viruses, yet the mechanism underlying this phenomenon remains unknown. Here we use theory and simulations to show that electrostatics provides one such mechanism, and that this is very general. Thus, we predict that the free energy of an RNA virus should increase by several thousands of $k_BT$ as the virion breaches an air-water interface. We also show that the fate of a virus approaching a generic liquid-liquid interface depends strongly on the detailed balance between interfacial and electrostatic forces, which can be tuned, for instance, by choosing different media to contact a virus-laden respiratory droplet. We propose that these results can be used to design effective strategies for surface disinfection. Intriguingly, tunability requires electrostatic and interfacial forces to scale similarly with viral size, which naturally occurs when charges are arranged in a double-shell distribution as in RNA viruses like influenza and all coronaviruses.
The mechanical unfolding of a simple RNA hairpin and of a 236--bases portion of the Tetrahymena thermophila ribozyme is studied by means of an Ising--like model. Phase diagrams and free energy landscapes are computed exactly and suggest a simple two--state behaviour for the hairpin and the presence of intermediate states for the ribozyme. Nonequilibrium simulations give the possible unfolding pathways for the ribozyme, and the dominant pathway corresponds to the experimentally observed one.
Log in to be able to interact and post comments
comments
Fetching comments
Sign in to be able to follow your search criteria
