Theory of density waves and organization of proteins in icosahedral virus capsids.

Understanding the physical principles underlying the structural organization of the proteinaceous viral shells is of major importance to advance antiviral strategies. Here, we develop a phenomenological thermodynamic theory, which considers structures of small and middle-size icosahedral viral shells as a result of condensation of a minimum number of protein density waves on a spherical surface. Each of these irreducible critical waves has icosahedral symmetry and can be expressed as a specific series of the spherical harmonics Ylm with the same wave number l. As we demonstrate, in small viral shells self-assembled from individual proteins, the maxima of one critical density wave determine the positions of proteins, while the spatial derivatives of the second one control the protein orientations on the shell surface. In contrast to the small shells, the middle-size ones are always formed from pentamers and hexamers (referred to as capsomers). Considering all such structures deposited in the Protein Data Bank, we unexpectedly found that the positions of capsomeres in these shells correspond to the maxima of interference patterns produced by no more than two critical waves with close wave numbers. This fact allows us to explain the observed limit size of the icosahedral shells assembled from pentamers and hexamers. We also construct nonequilibrium thermodynamic potentials describing the protein crystallization and discuss the reasons behind the specific handedness of the viral shells.

Close packings of identical proteins in small spherical capsids and similar proteinaceous shells.

Understanding the principles governing protein arrangement in viral capsids and structurally similar protein shells can enable the development of new antiviral strategies and the design of artificial protein cages for various applications. We study these principles within the context of the close packing problem, by analyzing dozens of small spherical shells assembled from a single type of protein. First, we use icosahedral spherical close packings containing 60T identical disks, where T ≤ 4, to rationalize the protein arrangement in twenty real icosahedral shells both satisfying and violating the paradigmatic Caspar-Klug model. We uncover a striking correspondence between the protein mass centers in the considered shells and the centers of disks in the close packings. To generalize the packing model, we consider proteins with a weak shape anisotropy and propose an interaction energy, minimization of which allows us to obtain spherical dense packings of slightly anisotropic structural units. In the case of strong anisotropy, we model the proteins as sequences of overlapping discs of different sizes, with minimum energy configuration not only resulting in packings, accurately reproducing locations and orientations of individual proteins, but also revealing that icosahedral packings that display the handedness of real capsids are energetically more favorable. Finally, by introducing effective disc charges, we rationalize the formation of inter-protein bonds in protein shells.

Integration of Cypoviruses into polyhedrin matrix.

Unlike in other viruses, in Cypoviruses the genome is doubly protected since their icosahedral capsids are embedded into a perfect polyhedrin crystal. Current experimental methods cannot resolve the resulting interface structure and we propose a symmetry-based approach to predict it. We reveal a remarkable match between the surfaces of Cypovirus and the outer polyhedrin matrix. The match arises due to the preservation of the common tetragonal symmetry, allowing perfect contacts of polyhedrin trimers with VP1 and VP5 capsid proteins. We highlight a crucial role of the VP5 proteins in embedding the Cypovirus into the polyhedrin matrix and discuss the relationship between the nucleoside triphosphatase activity of the proteins and their role in the superstructure formation. Additionally, we propose an electrostatic mechanism that drives the viral superstructure disassembly occurring in the alkaline environment of the insect intestines. Our study may underpin novel strategies for engineering proteinaceous nanocontainers in diverse biotechnological and chemical applications.

Hidden symmetry of the flavivirus protein shell and pH-controlled reconstruction of the viral surface.

Using recent Zika virus structural data we reveal a hidden symmetry of protein order in immature and mature flavivirus shells, violating the Caspar-Klug paradigmatic model of capsid structures. We show that proteins of the outer immature shell layer exhibit trihexagonal tiling, while proteins from inner and outer layers conjointly form a double-shelled close-packed structure, based on a common triangular spherical lattice. Within the proposed structural model, we furthermore rationalize the structural organization of misassembled non-infectious subviral particles that have no inner capsid. We consider a pH-controlled structural reconstruction of the outer shell from the trimeric to the dimeric state, and demonstrate that this transition, occurring during the virus maturation, can be induced by changes in protein charges at lower pH, leading to a decrease in the electrostatic interaction free energy. This transition could also be assisted by electrostatic attraction of shell proteins to the interposed lipid membrane substrate separating the shells.

Packing and trimer-to-dimer protein reconstruction in icosahedral viral shells with a single type of symmetrical structural unit.

Understanding the principles of protein packing and the mechanisms driving morphological transformations in virus shells (capsids) during their maturation can be pivotal for the development of new antiviral strategies. Here, we study how these principles and mechanisms manifest themselves in icosahedral viral capsids assembled from identical symmetric structural units (capsomeres). To rationalize such shells, we model capsomers as symmetrical groups of identical particles interacting with a short-range potential typical of the classic Tammes problem. The capsomere particles are assumed to retain their relative positions on the vertices of planar polygons placed on the spherical shell and to interact only with the particles from other capsomeres. Minimization of the interaction energy enforces equal distances between the nearest particles belonging to neighboring capsomeres and minimizes the number of different local environments. Thus, our model implements the Caspar and Klug quasi-equivalence principle and leads to packings strikingly similar to real capsids. We then study a reconstruction of protein trimers into dimers in a Flavivirus shell during its maturation, connecting the relevant structural changes with the modifications of the electrostatic charges of proteins, wrought by the oxidative switch in the bathing solution that is essential for the process. We highlight the key role of pr peptides in the shell reconstruction and show that the highly ordered arrangement of these subunits in the dimeric state is energetically favored at a low pH level. We also discuss the electrostatic mechanisms controlling the release of pr peptides in the last irreversible step of the maturation process.

Irreversible and reversible morphological changes in the φ6 capsid and similar viral shells: symmetry and micromechanics.

Understanding the physicochemical processes occurring in viruses during their maturation is of fundamental importance since only mature viruses can infect host cells. Here we consider the irreversible and reversible morphological changes that occur with the dodecahedral φ6 procapsid during the sequential packaging of 3 RNA segments forming the viral genome. It is shown that the dodecahedral shape of all the four observed capsid states is perfectly reproduced by a sphere radially deformed by only two irreducible spherical harmonics with icosahedral symmetry and wave numbers l = 6 and l = 10. The rotation of proteins around the 3-fold axes at the Procapsid → Intermediate 1 irreversible transformation is in fact also well described with the shear field containing only two irreducible harmonics with the same two wave numbers. The high stability of the Intermediate 1 state is discussed and the shapes of the Intermediate 2 state and Capsid (reversibly transforming back to the Intermediate 1 state) are shown to be mainly due to the isotropic pressure that the encapsidated RNA segments exert on the shell walls. The hidden symmetry of the capsid and the physicochemical features of the in vitro genome extraction from the viral shell are also elucidated.

Carbon nanotube sorting due to commensurate molecular wrapping.

Single-walled carbon nanotubes (SWCNTs) can be sorted by their structural parameters using organic molecules and polymers: some of which, demonstrating a profound affinity only for specific nanotubes, form dense coatings on them. Here, analyzing well-known examples of flavin group molecules and those of 2,4-dichlorophenoxyacetic acid, we show for the first time that successful formation of the considered coatings depends on the ability of molecules to wrap around the SWCNT in a commensurate way. Commensurability provides a decrease in the free energy of the resulting bilayer system and makes the coating much more stable. Concurrently, it strongly relates the nanotube chiral vector with the geometric characteristics of the adhering molecules, which leads to revealed selection rules. If they are not satisfied, the deposition of molecules does not occur or is insignificant. The proposed theory unambiguously explains known experimental results on the formation of spiral wrappings of SWCNTs by flavin group molecules and points out other organic molecules and polymers suitable for effective CNT sorting.

Hidden symmetry of the anomalous bluetongue virus capsid and its role in the infection process.

Clear understanding of the principles that control the arrangement of proteins and their self-assembly into viral shells is very important for the development of antiviral strategies. Here we consider the structural peculiarities and hidden symmetry of the anomalous bluetongue virus (BTV) capsid. Each of its three concentric shells violates the paradigmatic geometrical model of Caspar and Klug, which is otherwise well suited to describe most of the known icosahedral viral shells. As we show, three icosahedral spherical lattices, which are commensurate with each other and possess locally hexagonal (primitive or honeycomb) order, underlie the proteinaceous shells of the BTV capsid. This interpretation of the multishelled envelope allows us to discuss the so-called "symmetry mismatch" between its layers. We also analyze the structural stability of the considered spherical lattices on the basis of the classical theory of spherical packing and relate the proximity of the outer spherical lattice to destabilization with the fact that during infection of the cell VP2 trimers are detached from the surface of the BTV capsid. An electrostatic mechanism that can assist in this detachment is discussed in detail.

Anomalous small viral shells and simplest polyhedra with icosahedral symmetry: the rhombic triacontahedron case.

The development of antiviral strategies requires a clear understanding of the principles that control the protein arrangements in viral shells. Considered here are those capsids that violate the paradigmatic Caspar and Klug (CK) model, and it is shown that the important structural features of such anomalous shells from the Picobirnaviridae, Flaviviridae and Leviviridae families can be revealed by models in the form of spherical icosahedral packings of equivalent rhombic structural units (SUs). These SUs are composed of protein dimers forming the investigated capsids which, as shown here, are based on the rhombic triacontahedron (RT) geometry. How to modify the original CK approach in order to make it compatible with the considered rhombic tessellations of a sphere is also discussed. Analogies between capsids self-assembled from dimers and trimers are demonstrated. This analysis reveals the principles controlling the localization of receptor proteins (which recognize the host cell) on the capsid surface.

Static and dynamic hidden symmetries of icosahedral viral capsids.

Viral shells self-assemble from identical proteins, which tend to form equivalent environments in the resulting assembly. However, in icosahedral capsids containing more than 60 proteins, they are enforced to occupy not only the symmetrically equivalent locations but also the quasi-equivalent ones. Due to this important fact, static and dynamic symmetries of viral shells can include additional hidden components. Here, developing the Caspar and Klug ideas concerning the quasi-equivalence of protein environments, we derive the simplest hexagonal tilings, that in principle could correspond to the local protein order in viral shells, and apply the resulting theory to nucleocytoplasmic large dsDNA viruses. In addition, analyzing the dynamic symmetry of the P22 viral shell, we demonstrate that the collective critical modes responsible for the protein reorganization during the procapsid maturation are approximately equivalent to the normal modes of the isotropic spherical membrane with O(3) symmetry. Furthermore, we establish the relationship between the dynamic symmetry of the P22 procapsid and the protein arrangement regularities that appear only in the mature capsid.