The 2.1 \xc5 structure of protein F9 and its comparison to L1, two components of the conserved poxvirus entry-fusion complex

Ulrike S Diesterbeck,Apostolos G Gittis,Bernard Moss,David N Garboczi

doi:10.1038/s41598-018-34244-7

Ulrike S Diesterbeck, Apostolos G Gittis + Show 2 more

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https://doi.org/10.1038/s41598-018-34244-7

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Abstract

The poxvirus F9 protein is a component of the vaccinia virus entry fusion complex (EFC) which consists of 11 proteins. The EFC forms a unique apparatus among viral fusion proteins and complexes. We solved the atomic structure of the F9 ectodomain at 2.10 Å. A structural comparison to the ectodomain of the EFC protein L1 indicated a similar fold and organization, in which a bundle of five α-helices is packed against two pairs of β-strands. However, instead of the L1 myristoylation site and hydrophobic cavity, F9 possesses a protruding loop between α-helices α3 and α4 starting at Gly90. Gly90 is conserved in all poxviruses except Salmon gill poxvirus (SGPV) and Diachasmimorpha longicaudata entomopoxvirus. Phylogenetic sequence analysis of all Poxviridae F9 and L1 orthologs revealed the SGPV genome to contain the most distantly related F9 and L1 sequences compared to the vaccinia proteins studied here. The structural differences between F9 and L1 suggest functional adaptations during evolution from a common precursor that underlie the present requirement for each protein.

Highlights

Poxviruses are large enveloped DNA viruses that replicate in the cytoplasm and exist in three distinctive infectious forms: mature virions (MV), wrapped virions (WV), and extracellular virions (EV)[1]
Since each entry fusion complex (EFC) component has a putative transmembrane domain, they may be organized in a two-dimensional network on the MV membrane
The amino acid motif for adding a myristate moiety is conserved in all poxvirus orthologs of L1, except in Salmon gill poxvirus (SGPV)[21]

Summary

Introduction

Poxviruses are large enveloped DNA viruses that replicate in the cytoplasm and exist in three distinctive infectious forms: mature virions (MV), wrapped virions (WV), and extracellular virions (EV)[1]. The fusion apparatus is embedded in the MV membrane and consists of eleven proteins namely A1610, A2111, A2812, F913, G314, G915, H216, J517, L118, L519, and O320, which comprise the entry fusion complex (EFC). These proteins were identified in vaccinia virus (VACV) based on the inability of mutants to mediate entry and their interaction to form a complex. A human monoclonal antibody against F9 was isolated and characterized but did not neutralize virus in a plaque reduction test[31] Based on their primary structures, none of the EFC proteins resemble type 1, 2 or 3 entry proteins of other viruses. Homology based three-dimensional models of SGPV F9 and L1, the most distant orthologs relative to VACV, were generated and compared to the atomic structures of VACV F9 and L1

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