By means of two supramolecular systems - peptide amphiphiles engaged in hydrogen-bonded β-sheets, and chromophore amphiphiles driven to assemble by π-orbital overlaps - we show that the minima in the energy landscapes of supramolecular systems are defined by electrostatic repulsion and the ability of the dominant attractive forces to trap molecules in thermodynamically unfavourable configurations. These competing interactions can be selectively switched on and off, with the order of doing so determining the position of the final product in the energy landscape. Within the same energy landscape, the peptide-amphiphile system forms a thermodynamically favoured product characterized by long bundled fibres that promote biological cell adhesion and survival, and a metastable product characterized by short monodisperse fibres that interfere with adhesion and can lead to cell death. Our findings suggest that, in supramolecular systems, function and energy landscape are linked, superseding the more traditional connection between molecular design and function.
With few exceptions, the shells (capsids) of sphere-like viruses have the symmetry of an icosahedron and are composed of coat proteins (subunits) assembled in special motifs, the T-number structures. Although the synthesis of artificial protein cages is a rapidly developing area of materials science, the design criteria for self-assembled shells that can reproduce the remarkable properties of viral capsids are only beginning to be understood. We present here a minimal model for equilibrium capsid structure, introducing an explicit interaction between protein multimers (capsomers). Using Monte Carlo simulation we show that the model reproduces the main structures of viruses in vivo (T-number icosahedra) and important nonicosahedral structures (with octahedral and cubic symmetry) observed in vitro. Our model can also predict capsid strength and shed light on genome release mechanisms. Icosahedral symmetry is ubiquitous among spherical viruses (1). A classic example is the cowpea chlorotic mottle virus (CCMV), a well studied RNA virus with a shell composed of exactly 180 identical proteins (subunits) (2, 3). Fig. 1a is a cryo-transmission electron microscopy reconstruction showing 5-and 6-fold morphological units (capsomers), and Fig. 1b shows the arrangement of the individual subunits within the capsomers. The capsid has 6 5-fold rotation axes, 10 3-fold axes, and 15 2-fold axes, the symmetry elements of an icosahedron. The subunits can be divided into 12 capsomers that contain five subunits (pentamers) and 20 capsomers that contain six subunits (hexamers).The current understanding of sphere-like virus structures, like that adopted by CCMV, is based on the Caspar and Klug (CK) ''quasi-equivalence'' principle (4), which provides the foundation of modern structural virology. CK showed that closed icosahedral shells can be constructed from pentamers and hexamers by minimizing the number T of nonequivalent locations that subunits occupy, with the T-number adopting the particular integer values 1, 3, 4, 7, 12, 13, . . . (T ϭ h 2 ϩ k 2 ϩ hk, with h, k equal to nonnegative integers). These CK shells always contain 12 pentamers plus 10 (T-1) hexamers, and these structures have indeed been found to characterize a predominantly large fraction of sphere-like viruses (the CCMV capsid, for example, being a T ϭ 3 structure). Nevertheless, exceptions among WT capsids have been documented (5, 6), including the retroviruses like HIV (7); assembly of subunits with point mutations can also produce breakdown of CK-type capsid icosahedral symmetry (8).It is significant that the icosahedral point group generates the maximum enclosed volume for shells comprised of a given size subunit (4). But the fact that many viruses, including CCMV, self-assemble spontaneously from their molecular components under in vitro conditions (9) indicates that both icosahedral symmetry and the CK construction should be generic features of the free energy minima of aggregates of viral capsid proteins. Because of current computational limitations, direct eval...
We report a study of the in vitro self-assembly of virus-like particles formed by the capsid protein of cowpea chlorotic mottle virus and the anionic polymer poly(styrene sulfonate) (PSS) for five molecular masses ranging from 400 kDa to 3.4 MDa. The goal is to explore the effect on capsid size of the competition between the preferred curvature of the protein and the molecular mass of the packaged cargo. The capsid size distribution for each polymer was unimodal, but two distinct sizes were observed: 22 nm for the lower molecular masses, jumping to 27 nm at a molecular mass of 2 MDa. A model is provided for the formation of the virus-like particles that accounts for both the PSS and capsid protein self-interactions and the interactions between the protein and PSS. Our study suggests that the size of the encapsidated polymer cargo is the deciding factor for the selection of one distinct capsid size from several possible sizes with the same inherent symmetry.
A fundamental step in the replication of a viral particle is the self-assembly of its rigid shell (capsid) from its constituent proteins. Capsids play a vital role in genome replication and intercellular movement of viruses, and as such, understanding viral assembly has great potential in the development of new antiviral therapies and a systematic treatment of viral infection. In this article, we assume that nucleation is the underlying mechanism for self-assembly and combine the theoretical methods of the physics of equilibrium polymerization with those of the classical nucleation to develop a theory for the kinetics of virus self-assembly. We find expressions for the size of the critical capsid, the lag time, and the steady-state nucleation rate of capsids, and how they depend on both protein concentration and binding energy. The latter is a function of the acidity of the solution, the ionic strength, and the temperature, explaining why capsid nucleation is a sensitive function of the ambient conditions.
The protein shells, or capsids, of all sphere-like viruses adopt icosahedral symmetry. In the present paper we propose a statistical thermodynamic model for viral self-assembly. We find that icosahedral symmetry is not expected for viral capsids constructed from structurally identical protein subunits and that this symmetry requires (at least) two internal "switching" configurations of the protein. Our results indicate that icosahedral symmetry is not a generic consequence of free energy minimization but requires optimization of internal structural parameters of the capsid proteins.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.