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Influence of membrane composition on the binding and folding of a membrane lytic peptide from the non-enveloped flock house virus.

ABSTRACT: Using a combination of coarse-grained and atomistic molecular dynamics simulations we have investigated the membrane binding and folding properties of the membrane lytic peptide of Flock House virus (FHV). FHV is an animal virus and an excellent model system for studying cell entry mechanisms in non-enveloped viruses. FHV undergoes a maturation event where the 44 C-terminal amino acids are cleaved from the major capsid protein, forming the membrane lytic (?) peptides. Under acidic conditions, ? is released from the capsid interior allowing the peptides to bind and disrupt membranes. The first 21 N-terminal residues of ?, termed ?1, have been resolved in the FHV capsid structure and ?1 has been the subject of in vitro studies. ?1 is structurally dynamic as it adopts helical secondary structure inside the capsid and on membranes, but it is disordered in solution. In vitro studies have shown the binding free energies to POPC or POPG membranes are nearly equivalent, but binding to POPC is enthalpically driven, while POPG binding is entropically driven. Through coarse-grained and multiple microsecond all-atom simulations the membrane binding and folding properties of ?1 are investigated against homogeneous and heterogeneous bilayers to elucidate the dependence of the microenvironment on the structural properties of ?1. Our studies provide a rationale for the thermodynamic data and suggest binding of ?1 to POPG bilayers occurs in a disordered state, but ?1 must adopt a helical conformation when binding POPC bilayers.

SUBMITTER: Nangia S

PROVIDER: S-EPMC5482360 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Influence of membrane composition on the binding and folding of a membrane lytic peptide from the non-enveloped flock house virus.

Nangia Shivangi S May Eric R ER

Biochimica et biophysica acta. Biomembranes 20170407 7

Using a combination of coarse-grained and atomistic molecular dynamics simulations we have investigated the membrane binding and folding properties of the membrane lytic peptide of Flock House virus (FHV). FHV is an animal virus and an excellent model system for studying cell entry mechanisms in non-enveloped viruses. FHV undergoes a maturation event where the 44 C-terminal amino acids are cleaved from the major capsid protein, forming the membrane lytic (γ) peptides. Under acidic conditions, γ ...[more]

PMID: 28395954

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Project description:The larger segment (RNA 1) of the bipartite, positive-sense RNA genome of the nodavirus flock house virus encodes the viral RNA-dependent RNA polymerase. Two nonstructural viral proteins are made during the self-directed replication of this RNA: protein A (110 kDa), the translation product of RNA 1 itself, and protein B (11 kDa), the translation product of a subgenomic RNA (RNA 3) that is produced from RNA 1 during replication. To examine the roles of these proteins in RNA replication, specialized T7 transcription plasmids that contained wild-type or mutant copies of flock house virus RNA 1 cDNA were constructed and used in cells infected with the vaccinia virus-T7 RNA polymerase recombinant to make full-length transcripts that directed their own replication. Sequences in the primary transcripts that extended beyond the ends of the authentic RNA 1 sequence inhibited self-directed RNA replication, but plasmids that were constructed to minimize these terminal extensions produced primary transcripts that replicated as abundantly as authentic RNA 1. Truncation or mutation of the open reading frame for protein A eliminated self-directed replication, although the mutant RNA 1 remained a competent template for replication by wild-type protein A supplied in trans. These results showed that protein A was essential for RNA replication and that the process was not inseparably coupled to complete translation of the template. In contrast, protein B could be eliminated without inhibiting replication by mutations that disrupted the second of the two overlapping open reading frames on RNA 3. Furthermore, a mutant of RNA 1 in which the first nucleotide of the RNA 3 region was changed from G to U replicated at levels as high as those of the wild type without making either RNA 3 or protein B. However, diminishing replication levels were observed during subsequent replicative passages of RNA from both the mutants that could not make protein B. Roles for this protein that could account for the subtle phenotype of these mutants are discussed.

Dataset Information

Influence of membrane composition on the binding and folding of a membrane lytic peptide from the non-enveloped flock house virus.

Publications

Influence of membrane composition on the binding and folding of a membrane lytic peptide from the non-enveloped flock house virus.

Similar Datasets

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