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1.A.59 The Bursal Disease Virus Pore-Forming Peptide, Pep46 (Pep46) Family

Double-stranded RNA (dsRNA) virions constitute transcriptionally competent machines that must translocate across cell membranes to function within the cytoplasm. Birnaviruses are unique among dsRNA viruses because they possess a single shell competent for entry. Infectious bursal disease virus, a non-enveloped virus, possesses a capsid-associated peptide that deforms and perforates biological membranes. One of its four structural peptides, pep46 (a 46-amino-acid amphiphillic peptide) deforms synthetic membranes and induces pores visualized by electron cryomicroscopy, having a diameter of less than 10 nm. Using both biological and synthetic membranes, the pore-forming domain of pep46 was identified as its N terminal moiety (pep22) (Galloux et al., 2007). The N and C termini of pep22 are shown to be accessible during membrane destabilization and pore formation. Pep46 inserts into micelles and displays a cis-trans proline isomerization at position 16 that is required for pore formation. The amphiphilicity and proline isomerization of pep46 are both essential to the viral cycle. Virus infectivity and its membrane activity (probably because of the release of pep46 from virions) are controlled differently by calcium concentration, suggesting that entry is performed in two steps, endocytosis followed by endosome permeablization. The entry pathway of infectious bursal disease virus involves (1) entry into endosomes, (2) the lowering of the calcium concentration in endosomes containing viruses, and (3) the release of pep46 which induces the formation of pores in the endosomal membrane. The NMR structure of Pep46 is known.

The transport reaction catalyzed by Pep46 is:

ions (out) ions (in).

References associated with 1.A.59 family:

Galloux, M., S. Libersou, I.D. Alves, R. Marquant, G.F. Salgado, H. Rezaei, J. Lepault, B. Delmas, S. Bouaziz, and N. Morellet. (2010). NMR structure of a viral peptide inserted in artificial membranes: a view on the early steps of the birnavirus entry process. J. Biol. Chem. 285: 19409-19421. 20385550
Galloux, M., S. Libersou, N. Morellet, S. Bouaziz, B. Da Costa, M. Ouldali, J. Lepault, and B. Delmas. (2007). Infectious bursal disease virus, a non-enveloped virus, possesses a capsid-associated peptide that deforms and perforates biological membranes. J. Biol. Chem. 282: 20774-20784. 17488723