Structural Biochemistry, Diverse Interctions of retroviral Gag proteins with RNAs

Introduction

Retroviruses are created by Gag, a single virus-encoded protein. Assembling an infectious particle means there are very diverse interactions (specific and nonspecific) between Gag proteins and RNA. These interactions are vital for the particle construction, packing of viral RNA in the particle, and how the primer is placed for viral DNA synthesis.

Gag proteins: the building blocks of retroviruses

Retroviruses are composed of 6 genera (alpha-, beta-, gamma-, delta-, epsilon-, and lenti-retrovirsuses) and also a subfamily called Spumaviridae. Th Gag protein is the building block for retrovirus particles; expression of this protein allows for efficient assembly of virus-like particles in most, if not all, mammalian cells. When viruses are being assembled, Gag proteins interact with lipids in the plasma membrane with RNAs and other Gag molecules. These interactions involve the formation of the particle, selecion of what RNA species will be included in the particle, and the refolding of the packages RNAs.

A nonspecific interaction with RNAs drives virus particle assembly

Purified, recombinant Gag proteins are soluble in aqueous solutions so they aren't interested for protein-protein interactions that needs to occur for virus particle formation. However, if a single-stranded nucleic acid is added, it triggers in vitro assembly on the Gag proteins into VLPs.
In vivo, particle assembly is dependent on Gag-nucleic acids (NA) interactions because NAs are about 20-40 nucleotides, so they can support assembly in vitro. The NAs are so short, though, that they can only bind to a few Gag molecules.

The NC domain of Gag is where the site of interaction is at with NAs.When the NC domain binds with NA, the conformation is altered of the capsid domain. This ultimately exposes new interfaces for protein-protein interaction.

In many retroviruses, the NC domain of Gag is most attracted to RNA.However, the matrix domain at the N-terminus is positively charged and is also able to interact with RNAs.

Reference

Rein, Alan, et al. "Diverse interactions of retroviral Gag proteins with RNAs" Trends in Biochemical Sciences 36.7 (2011) 373-379. Academic Search Complete. Web. 21 Nov. 2012.

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