Dataset Information

A viral scaffolding protein triggers portal ring oligomerization and incorporation during procapsid assembly.

ABSTRACT: Most double-stranded DNA viruses package genetic material into empty precursor capsids (or procapsids) through a dodecameric portal protein complex that occupies 1 of the 12 vertices of the icosahedral lattice. Inhibiting incorporation of the portal complex prevents the formation of infectious virions, making this step an excellent target for antiviral drugs. The mechanism by which a sole portal assembly is selectively incorporated at the special vertex is unclear. We recently showed that, as part of the DNA packaging process for bacteriophage P22, the dodecameric procapsid portal changes conformation to a mature virion state. We report that preformed dodecameric rings of P22 portal protein, as opposed to portal monomers, incorporate into nascent procapsids, with preference for the procapsid portal conformation. Finally, a novel role for P22 scaffolding protein in triggering portal ring formation from portal monomers is elucidated and validated by incorporating de novo assembled portal rings into procapsids.

SUBMITTER: Motwani T

PROVIDER: S-EPMC5529062 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A viral scaffolding protein triggers portal ring oligomerization and incorporation during procapsid assembly.

Motwani Tina T Lokareddy Ravi K RK Dunbar Carmen A CA Cortines Juliana R JR Jarrold Martin F MF Cingolani Gino G Teschke Carolyn M CM

Science advances 20170726 7

Most double-stranded DNA viruses package genetic material into empty precursor capsids (or procapsids) through a dodecameric portal protein complex that occupies 1 of the 12 vertices of the icosahedral lattice. Inhibiting incorporation of the portal complex prevents the formation of infectious virions, making this step an excellent target for antiviral drugs. The mechanism by which a sole portal assembly is selectively incorporated at the special vertex is unclear. We recently showed that, as pa ...[more]

PMID: 28782023

Similar Datasets

Project description:During ?X174 morphogenesis, 240 copies of the external scaffolding protein D organize 12 pentameric assembly intermediates into procapsids, a reaction reconstituted in vitro In previous studies, ?X174 strains resistant to exogenously expressed dominant lethal D genes were experimentally evolved. Resistance was achieved by the stepwise acquisition of coat protein mutations. Once resistance was established, a stimulatory D protein mutation that greatly increased strain fitness arose. In this study, in vitro biophysical and biochemical methods were utilized to elucidate the mechanistic details and evolutionary trade-offs created by the resistance mutations. The kinetics of procapsid formation was analyzed in vitro using wild-type, inhibitory, and experimentally evolved coat and scaffolding proteins. Our data suggest that viral fitness is correlated with in vitro assembly kinetics and demonstrate that in vivo experimental evolution can be analyzed within an in vitro biophysical context. IMPORTANCE:Experimental evolution is an extremely valuable tool. Comparisons between ancestral and evolved genotypes suggest hypotheses regarding adaptive mechanisms. However, it is not always possible to rigorously test these hypotheses in vivo We applied in vitro biophysical and biochemical methods to elucidate the mechanistic details that allowed an experimentally evolved virus to become resistant to an antiviral protein and then evolve a productive use for that protein. Moreover, our results indicate that the respective roles of scaffolding and coat proteins may have been redistributed during the evolution of a two-scaffolding-protein system. In one-scaffolding-protein virus assembly systems, coat proteins promiscuously interact to form heterogeneous aberrant structures in the absence of scaffolding proteins. Thus, the scaffolding protein controls fidelity. During ?X174 assembly, the external scaffolding protein acts like a coat protein, self-associating into large aberrant spherical structures in the absence of coat protein, whereas the coat protein appears to control fidelity.

Dataset Information

A viral scaffolding protein triggers portal ring oligomerization and incorporation during procapsid assembly.

Publications

A viral scaffolding protein triggers portal ring oligomerization and incorporation during procapsid assembly.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets