TMV Particles: The Journey From Fundamental Studies to Bionanotechnology Applications

Abstract

Ever since its initial characterization in the 19th century, tobacco mosaic virus (TMV) has played a prominent role in the development of modern virology and molecular biology. In particular, research on the three-dimensional structure of the virus particles and the mechanism by which these assemble from their constituent protein and RNA components has made TMV a paradigm for our current view of the morphogenesis of self-assembling structures, including viral particles. More recently, this knowledge has been applied to the development of novel reagents and structures for applications in biomedicine and bionanotechnology. In this article, we review how fundamental science has led to TMV being at the vanguard of these new technologies.

Keywords: Chemical modification; Coat protein; Nanorings; Nanostars; Origin of assembly; Peptide presentation; Self-assembly.

Fig. 1

TMV—the basics. (A) Diagram of the genomic RNA showing the three open reading frames (ORFs) for the polymerase, movement protein (MP), and coat protein (CP). The position of the leaky UAG codon within the polymerase ORF is indicated. The sites for insertion into a surface loop (L) and the C-terminus (C) are shown by red arrows above the CP ORF. (B) Tertiary structure of an isolated CP subunit. (C) Structure of the two-layer disk as seen in the crystal structure of the four-layer aggregate described by Bhyravbhatla et al. (1998). (D) View down the assembled nucleoprotein helix. (E) View along the TMV rod. In each case the exposed surface loop and C-terminus of the CP are indicated in red.

Fig. 2

Examples of applications of TMV particles. The image in the center shows a TMV rod assembling via the traveling loop mechanism. The various applications are described throughout the text. Reproduced under the terms of the Creative Commons Attribution 2.0 International Public License from Koch et al. (2016).

Fig. 3

Redesigning the shape of TMV-derived nanoobjects. RNA-directed growth and combination of nanotubular structures using in vitro technology. (A) Nanorings assembled and stabilized by help of a 204-nt long, OAS-containing RNA. (B) Kinked and branched boomerang up to tetrapod products accessed through colliding nanotube domain ends growing on RNA scaffolds with two up to five OAS. (C) TMV-like nanorods with selectively addressable longitudinal subdomains, obtained either by serial assembly with limited amounts of distinct CP species or in a nanometrically defined manner by a DNA blocking element-enabled stop-and-go procedure. Bottom row: Hybrid assemblies with nonbiomolecular core structures: (D) nanostars with TMV-deduced arms, grown by bottom-up technology on DNA-programmed gold beads. (E₁–E₄) Expanded nanoarchitectures with up to four TMV arms linked covalently to tetrahedral adamantane-based organic cores.