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

Abstract

Using recent Zika virus structural data we reveal a hidden symmetry of protein order in immature and mature flavivirus shells, which violates the Caspar-Klug paradigmatic model of capsid structures. We...

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

“…Virus capsids of the Flaviviridae family have 180 proteins, which is allowed by the CK model, but the mature structure of these shells contains neither pentamers nor hexamers and consists of 90 dimers. 29 Structures of such anomalous (violating the CK model), small (containing no more than 240 proteins) icosahedral spherical capsids can be rationalized within the generalized CK model. 18 We follow this approach, and in the rest of the paper indices (h,k) define SLs whose positions correspond to individual proteins rather than capsomeres in the CK model.…”

Integration of Cypoviruses into polyhedrin matrix

“…Changes in pH of the bathing solution can lead specifically to substantial changes in electrostatic charge of the viral proteins 31 that can in its turn drive global structural rearrangements of protein assemblies. 32,33 Motivated by the experimental findings 4,14,34 that disassembly of Cypovirus polyhedra and release of the embedded virions are strongly dependent on the acidity of the surrounding solution, we now examine the molecular details of how the increase in pH affects interactions between viral proteins and polyhedrin trimers.…”

“…Our simple coarse-grained electrostatic model considers each protein as a set of point charges that correspond to solvent-exposed ionizable amino acids. 31,32,34 We calculate their partial charges using the Henderson–Hasselbalch equation: 28,38,39 where the sign is defined by the type of AA: plus is used for basic amino acids (Arg, His, Lys) and minus for the acidic ones (Asp, Glu, Tyr). Values of the acid–base dissociation constant p K a i of AAs are taken from ref.…”

“…Standardly the screening length under physiological conditions can be estimated to be l D z 1 nm. 32,33,41 First, let us discuss how the trimer charge and electrostatic energy of CPV1 polyhedrin crystal (5GQL) change with the increasing pH. Fig.…”

“…Here, within the framework of the developed model, we took the same values of the effective screening length l D and permittivity 3 (see Methods) that we previously used to model other protein systems. 32,33 More accurate estimations can be obtained by solving complex nonlinear equations describing the distribution of electrostatic potential in the nonhomogeneous dielectric medium. 42 Even without nding explicit solution of this problem one can assume that due to the high density of the polyhedrin crystal, the effective permittivity could be substantially lower and the effective screening length substantially higher than our initial estimate.…”