Portal Protein: The Orchestrator of Capsid Assembly for the dsDNA Tailed Bacteriophages and Herpesviruses

Abstract

Tailed, double-stranded DNA bacteriophages provide a well-characterized model system for the study of viral assembly, especially for herpesviruses and adenoviruses. A wealth of genetic, structural, and biochemical work has allowed for the development of assembly models and an understanding of the DNA packaging process. The portal complex is an essential player in all aspects of bacteriophage and herpesvirus assembly. Despite having low sequence similarity, portal structures across bacteriophages share the portal fold and maintain a conserved function. Due to their dynamic role, portal proteins are surprisingly plastic, and their conformations change for each stage of assembly. Because the maturation process is dependent on the portal protein, researchers have been working to validate this protein as a potential antiviral drug target. Here we review recent work on the role of portal complexes in capsid assembly, including DNA packaging, as well as portal ring assembly and incorporation and analysis of portal structures.

Keywords: DNA packaging; bacteriophage assembly; portal fold; virus assembly.

Figure 1

Bacteriophage P22 assembly pathway. Coat monomers, scaffolding protein, and portal monomers make up a nucleation complex, forming the portal ring around which the coat protein shell can be assembled by scaffolding protein. The ejection proteins are incorporated into the procapsid prior to DNA packaging by terminase proteins. Pressure from DNA induces a conformational change in the capsid and portal protein facilitating the dissociation of the terminase complex and addition of the tail machinery.

Figure 2

The tryptophan belt (red spheres) shown in portal proteins from P22 (5JJ3), Phi29 (1FOU), T4 (3JA7), SPP1 (2JES), G20c (4ZJN), and HSV-1 (6OD7). The portal complexes shown are all in the mature virion conformation. The well-conserved ring of tryptophan residues in the portal wing domains are important for portal interactions with scaffolding protein and ring assembly.

Figure 3

(a) Portal ring structures from Phi29 (1FOU), SPP1 (2JES), T4 (3JA7), and P22 (5JJ3) from side and top views (arrows indicate internal pore diameter). (b) Chart summarizing the molecular weight and pore diameters of the portal complexes.

Figure 4

P22 procapsid (left panel) and mature virion (right panel) portal structures. The monomers (a,b) have been colored by domain: barrel (blue), crown (red), wing (cyan), stem (gray), and clip (green). The tunnel (*) and channel (**) loops have been denoted. The top (c,d) and side (e,f) views of the procapsid and mature virion portal structures are shown with the hammer (red) and trigger loops (cyan) highlighted.

Figure 5

Portal complexes from P22, SPP1, Phi29, and T4 side and top views shown as gray spheres, with central helices highlighted in red. The core helices are important for oligomerization as well as DNA ejection and the conformational changes required for the maturation and ejection processes.