Reovirus protein σ1: From cell attachment to protein oligomerization and folding mechanisms

Abstract

The reovirus cell attachment protein sigma 1 is a lollipop-shaped structure with the fibrous tail anchored to the virion. Since it interacts with the cell receptor, sigma 1 is a major determinant of reovirus infectivity and tissue tropism. Studies on its structure-function relationships have been facilitated by the fact that protein sigma 1 produced in any expression system is capable of binding to cell receptors. The use of site-specific and deletion mutants has led to the identification and characterization of its virion anchorage and receptor binding domains. Studies on the oligomeric status of sigma 1 have revealed that sigma 1 is a homotrimer and that two independent trimerization events at different loci (the N- and C-terminal halves, respectively) of the protein, are involved in its generation. This also accounts for a clearly demonstrable dominant negative effect by a mutant subunit in a wild-type/mutant sigma 1 heterotrimer. Current efforts are focused on the involvement of chaperones in the generation of sigma 1 and on events that take place upon sigma 1 binding to the cell receptor. Protein sigma 1 has therefore become an excellent model system for the study of both virus attachment and protein oligomerization and folding mechanisms.

Unfolding studies of human adenovirus type 2 fibre trimers

“…The in vitro translation observations also suggest that fibre assembly might occur in the cytoplasm of the infected cell. Quite extensive studies have been carried out on the folding of viral spikes inside procaryotic cells [1, 2, 38] or viral membrane glycoproteins proteins inside eukaryotic cells [39]; however very few studies have been made of the folding of viral proteins assembled in the eukaryotic cytoplasm, with the exception of reovirus sigma protein [40]. In that respect, adenovirus fibres might serve as a model system for studying the intracytoplasmic protein folding, misfolding or misassembly inside eukaryotic cells.…”

Transport of artificial virus-like nanocarriers through intestinal monolayers via microfold cells

“…Hence, these AVNs can serve as effective transport vehicles for oral vaccines. AVN construction required purification of σ1, preparation of gold nanocages, and linkage of σ1 to the nanocage surface in an appropriate conformation where the head domain (C-terminal portion) 7 of σ1 can interact with α2-3 sialic acid located on the M cell apical surface. 6 With the nanocarriers being surface-functionalized with T1L σ1, conventional 2-D spherical nanoparticles were not good candidates as the outer surface would no longer be available for payload loading.…”

Structure, function and immune evasion strategies of aquareoviruses, with focus on grass carp reovirus

“…Viral entry is the first step of virion replication and assembly in a host cell, and viruses adopt various mechanisms to cross the host cell membrane barrier, including receptor binding, plasma membrane fusion and endocytosis et al 66 For non-enveloped dsRNA virus MRVs, σ1 protein encoded by segment 7 is an attachment protein that forms a filamentous trimer extended from the turret trimer, and the head-and-tail structure formed by σ1 protein is required for binding receptors, including the sialic acid and junctional adhesion molecule-A (JAM-A). 67,68 The N-terminal tail domain forms an α-helical coiled-coil structure partially inserted into turret protein, and the middle body domain consists of β-spiral repeat motif and an inserted short α-helical coiled-coil motif.…”