1.A.61 The Insect Nodavirus Channel-forming Chain F (Gamma-Peptide) Family

Membrane translocation of the single-stranded RNA genomes of nodaviruses has been proposed to be mediated by direct lipid-protein interactions between a post-assembly autocatalytic cleavage product from the capsomere and the target membrane. A 21-residue Met-->Nle (norleucine) variant of the amino-terminal helical domain (denoted here as gamma1) of the cleavage peptide in Flock House nodavirus (FHV) was synthesized (Bong et al., 1999). The synthetic peptide gamma1 increases membrane permeability to hydrophilic solutes, as judged by fluorescence experiments with liposome-encapsulated dyes and ion-conductance measurements. The helical domain of the FHV cleavage product partitions spontaneously into lipid bilayers and increases membrane permeability, consistent with the postulated mechanism for viral genome translocation (Janshoff et al., 1999). The existence of a membrane-binding domain in the FHV cleavage sequence suggests peptide-triggered disruption of the endosomal membrane as a prelude to viral uncoating in the host cytoplasm (Bong et al., 1999).

The reactions catalyzed by gamma-peptide are:

small molecules/ions/nucleocapsid (out) small molecules/ions/nucleocapsid (in)


 

References:

Bong D.T., C. Steinem, A. Janshoff, J.E. Johnson, M. Reza Ghadiri. (1999). A Highly Membrane-Active Peptide in Flock House Virus: Implications for the Mechanism of Nodavirus Infection. Chem Biol. 6(7):473-481.

Janshoff A., D.T. Bong, C. Steinem, J.E. Johnson, and M.R. Ghadiri. (1999). An Animal Virus-Derived Peptide Switches Membrane Morphology: Possible Relevance to Nodaviral Transfection Processes. Biochemistry. 38(17):5328-5336.

Nangia, S., K.J. Boyd, and E.R. May. (2019). Molecular dynamics study of membrane permeabilization by wild-type and mutant lytic peptides from the non-enveloped flock house virus. Biochim. Biophys. Acta. Biomembr 183102. [Epub: Ahead of Print]

Examples:

TC#NameOrganismal TypeExample
1.A.61.1.1Chain F or gamma-peptide (44aas; 1TMS), membrane active domain (Bong et al., 1999)VirusesChain F of Flock House Nodamura Virus (P12871)
 
1.A.61.1.2

Flock House virus (FHV) capsid protein-α of 407 aas; Its C-terminal 44 aas comprise a lytic peptide, one of the γ-peptides that inserts into endomembranes forming pores. Capsid protein alpha self-assembles to form an icosahedral procapsid with a T=3 symmetry, about 30 nm in diameter, and consisting of 60 capsid proteins trimers. 240 calcium ions are incorporated per capsid during assembly. The capsid encapsulates the two genomic RNAs. Capsid maturation occurs via autoproteolytic cleavage of capsid protein alpha, generating capsid protein beta and the membrane-active peptide gamma.  Peptide γ is a membrane-permeabilizing peptide produced during virus maturation, thereby creating the infectious virion. After endocytosis into the host cell, peptide gamma is exposed in endosomes, where it permeabilizes the endosomal membrane, facilitating translocation of viral capsid or RNA into the cytoplasm.  Nangia et al. 2019 shed light on the actions of varied forms of the FHV lytic peptide including membrane insertion, trans-membrane stability, peptide oligomerization, water permeation activity and dynamic pore formation.

 

α-capsid protein, including the C-terminal γ-peptide of Flock House virus (FHV)