Building the Machines: Scaffolding Protein Functions During Bacteriophage Morphogenesis

Abstract

For a machine to function, it must first be assembled. The morphogenesis of the simplest icosahedral virus would require only 60 copies of a single capsid protein to coalesce. If the capsid protein's structure could be entirely dedicated to this endeavor, the morphogenetic mechanism would be relatively uncomplicated. However, capsid proteins have had to evolve other functions, such as receptor recognition, immune system evasion, and the incorporation of other structure proteins, which can detract from efficient assembly. Moreover, evolution has mandated that viruses obtain additional proteins that allow them to adapt to their hosts or to more effectively compete in their respective niches. Consequently, genomes have increased in size, which has required capsids to do likewise. This, in turn, has lead to more complex icosahedral geometries. These challenges have driven the evolution of scaffolding proteins, which mediate, catalyze, and promote proper virus assembly. The mechanisms by which these proteins perform their functions are discussed in this review.

Molecular architecture of tailed double-stranded DNA phages

“…2). [11][12][13] The head assembly typically starts at the portal vertex by copolymerization of the scaffolding proteins and the major capsid protein leading to formation of the capsid precursors called prohead (or procapsid). The prohead consists of the portal protein, the internal scaffolding core, and the outer major capsid protein shell surrounding the core.…”

Effects of an Early Conformational Switch Defect during ϕX174 Morphogenesis Are Belatedly Manifested Late in the Assembly Pathway

“…These switches reduce the thermodynamic barriers in the productive pathway relative to those that promote off-pathway reactions (1)(2)(3). Since many assembly systems involve the rapid addition of small elongation units to short-lived nucleation complexes, morphogenesis is typically divided into three stages: coat protein binding, nucleation, and elongation (1)(2)(3).…”

“…These switches reduce the thermodynamic barriers in the productive pathway relative to those that promote off-pathway reactions (1)(2)(3). Since many assembly systems involve the rapid addition of small elongation units to short-lived nucleation complexes, morphogenesis is typically divided into three stages: coat protein binding, nucleation, and elongation (1)(2)(3). While the absence of coat protein binding can be easily distinguished from other defects (4)(5)(6), the fluid nature of assembly can obscure the differences between defects in the later stages.…”

Unraveling the Role of the C-terminal Helix Turn Helix of the Coat-binding Domain of Bacteriophage P22 Scaffolding Protein

“…Many virions are built by first assembling intermediate structures called procapsids into which nucleic acid is subsequently packaged, and in many of these a scaffolding protein is required to assemble properly shaped procapsids. Scaffolding proteins act as molecular chaperones for assembly and are called "scaffolding" proteins because they are not present in the mature virion but are present in procapsids (1)(2)(3). Most large dsDNA viruses such as bacteriophages P22, ⌽29, P2, SPP1, T7, T4, and and the herpesviruses have scaffolding proteins that are stably present within the interior of the procapsid but are released from these particles at or before the time of nucleic acid packaging.…”