The remarkable viral portal vertex: structure and a plausible model for mechanism

Abstract

Many icosahedral viruses including tailed bacteriophages and herpes viruses have a unique portal vertex where a dodecameric protein ring is associated with a fivefold capsid shell. While the peripheral regions of the portal ring are involved in capsid assembly, its central channel is used to transport DNA into and out of capsid during genome packaging and infection. Though the atomic structure of this highly conserved, turbine-shaped, portal is known for nearly two decades, its molecular mechanism remains a mystery. Recent high-resolution in situ structures reveal various conformational states of the portal and the asymmetric interactions between the 12-fold portal and the fivefold capsid. These lead to a valve-like mechanism for this symmetry-mismatched portal vertex that regulates DNA flow through the channel, a critical function for high fidelity assembly of an infectious virion.

Figure 1.

Structures of the portal assemblies from different tailed phages and herpes viruses. For each portal, the side and top views are shown with the subunits alternately colored green and magenta. In the case of the phage SPP1 portal, one subunit is colored black because the recombinantly produced portal used for structure determination was a 13-mer. The individual subunits of the portal proteins are shown in rainbow colors, ranging from blue at the N-terminus to red at the C-terminus. The Protein Data Bank identification numbers are shown in parentheses.

Figure 2.

Domains of representative portal proteins from phage T4, phage T7, and Kaposi’s sarcoma associated herpesvirus (KSHV). The crown region (referred to as “wall” in the case of KSHV) of each portal is colored orange, wing domain is green, the stem region is blue, and the clip region is magenta. The barrel region of the T7 portal is colored red. For phage T4, the capsid protein subunits associated with the portal at the five-fold vertex are shown in gray. For phage T7, the tail adaptor (“neck”) protein attached to the portal is shown in cyan, and the tail nozzle protein is shown in grey. The clip domain of KSHV portal contains a large ∼130-aa “turret” insertion consisting of tentacle helices. The points of this unmodelled insertion are indicated by arrows.

Figure 3.

Symmetry mismatch accommodation in the portal-capsid interface of phage T4. (a) The flexible components of the portal subunits that make contacts with the capsid and their surrounding capsid environment. The capsid proteins are colored in pink, cyan or gray. The five surrounding capsid protein subunits (pink) are labeled as “S” subunits and the five that are more distant to portal (cyan) are labeled as “D” subunits. The portal subunits are shown in both surface view and ribbon diagram and labeled 1–12. The surface view is shown semitransparently. Alternate portal subunits are colored in blue or orange. For the portal subunits, only the regions that make contacts with the capsid are shown. The potential methionine-metal clusters that anchor the portal to the capsid are indicated using red arrows and the corresponding portal subunits are labeled as p and p+5. (b-e) Superimposition of the twelve portal subunits showing high conformational variations in their capsid-interfacing regions. (f, g) The potential methionine-metal clusters form between the N-whisker methionine (M1) of portal subunits p or p+5, and methionines M98 and M284 and histidine H282 of the capsid protein subunits. The figure is adapted from Fang et al. 2020.

Figure 4.

The Open and Closed conformational states of the portal. (a) The open states of the portals of thermophilic bacteriophage P23–45 (PDB ID: 6QJT) [29] and phage T7 (PDB ID: 7BP0) [27]. (b) The closed states of the portals of phage G20c (PDB ID: 6IBG) [31] and T7 (PDB ID: 7BOU) [27].