arXiv subjects

T. Keef

Publications and source records attributed to T. Keef.

4 recordsLinked to original sources

arXiv2005

A new series of polyhedra as blueprints for viral capsids in the family of Papovaviridae

In a seminal paper Caspar and Klug established a theory that provides a family of polyhedra as blueprints for the structural organisation of viral capsids. In particular, they encode the locations of the proteins in the shells that encapsulate, and hence provide protection for, the viral genome. Despite of its huge success and numerous applications in virology experimental results have provided evidence for the fact that the theory is too restrictive to describe all known viruses. Especially, the family of Papovaviridae, which contains cancer-causing viruses, falls out of the scope of this theory. In a recent paper we have shown that certain members of the family of Papovaviridae can be described via tilings. In this paper, we develop a comprehensive mathematical framework for the derivation of all surface structures of viral particles in this family. We show that this formalism fixes the structure and relative sizes of all particles collectively so that there exists only one scaling factor that relates the sizes of all particles with their biological counterparts. The series of polyhedra derived here complements the Caspar-Klug family of polyhedra. It is the first mathematical result that provides a common organisational principle for different types of viral particles in the family of Papovaviridae and paves the way for an understanding of Papovaviridae polymorphism. Moreover, it provides crucial input for the construction of assembly models.

q-bio.BM↗

arXiv2005

Classification of capped tubular viral particles in the family of Papovaviridae

A vital constituent of a virus is its protein shell, called the viral capsid, that encapsulates and hence provides protection for the viral genome. Viral capsids are usually spherical, and for a significant number of viruses exhibit overall icosahedral symmetry. The corresponding surface lattices, that encode the locations of the capsid proteins and intersubunit bonds, can be modelled by Viral Tiling Theory. It has been shown in vitro that under a variation of the experimental boundary conditions, such as the pH value and salt concentration, tubular particles may appear instead of, or in addition to, spherical ones. In order to develop models that describe the simultaneous assembly of both spherical and tubular variants, and hence study the possibility of triggering tubular malformations as a means of interference with the replication mechanism, Viral Tiling Theory has to be extended to include tubular lattices with end caps. This is done here for the case of Papovaviridae, which play a distinguished role from the viral structural point of view as they correspond to all pentamer lattices, i.e. lattices formed from clusters of five protein subunits throughout. These results pave the way for a generalisation of recently developed assembly models.

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arXiv2005

Master equation approach to the assembly of viral capsids

The distribution of inequivalent geometries occurring during self-assembly of the major capsid protein in thermodynamic equilibrium is determined based on a master equation approach. These results are implemented to characterize the assembly of SV40 virus and to obtain information on the putative pathways controlling the progressive build-up of the SV40 capsid. The experimental testability of the predictions is assessed and an analysis of the geometries of the assembly intermediates on the dominant pathways is used to identify targets for antiviral drug design.

q-bio.BM↗

arXiv2005

Assembly Models for Papovaviridae based on Tiling Theory

A vital constituent of a virus is its protein shell, called the viral capsid, that encapsulates and hence provides protection for the viral genome. Assembly models are developed for viral capsids built from protein building blocks that can assume different local bonding structures in the capsid. This situation occurs, for example, for viruses in the family of Papovaviridae, which are linked to cancer and are hence of particular interest for the health sector. More specifically, the viral capsids of the (pseudo-) T=7 particles in this family consist of pentamers that exhibit two different types of bonding structures. While this scenario cannot be described mathematically in terms of Caspar-Klug Theory (Caspar and Klug 1962), it can be modelled via tiling theory (Twarock 2004). The latter is used to encode the local bonding environment of the building blocks in a combinatorial structure, called the assembly tree, which is a basic ingredient in the derivation of assembly models for Papovaviridae along the lines of the equilibrium approach of Zlotnick (Zlotnick 1994). A phase space formalism is introduced to characterize the changes in the assembly pathways and intermediates triggered by the variations in the association energies characterizing the bonds between the building blocks in the capsid. Furthermore, the assembly pathways and concentrations of the statistically dominant assembly intermediates are determined. The example of Simian Virus 40 is discussed in detail.

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