Polyomavirus capsid protein (VP1)
From CFGparadigms
Polyomaviruses are a group of small, non-enveloped DNA viruses that can infect birds, rodents, and primates. Members of the group include simian virus 40 (SV40) and murine polyomavirus (mPyV) as well as a number of human polyomaviruses such as the BK and JC viruses (BKV and JCV, respectively). Recently, a new human polyomavirus was found to be linked to Merkel cell carcinoma, an aggressive type of skin cancer (Feng et al., 2008). All polyomavirus capsids are constructed from 360 copies of the major coat protein, VP1, arranged in pentamers on a T=7 icosahedral lattice (Liddington et al., 1991). The cell-surface receptors for SV40, mPyV, BKV, JCV, and possibly other polyomaviruses are gangliosides, which are complex, sialic acid-containing sphingolipids that reside primarily in lipid rafts. SV40 uses the ganglioside GM1, BKV binds GD1b and GT1b, and mPyV attaches to GD1a and GT1b (Tsai et al., 2003; Low et al., 2006). Crystal structures are available for complete mPyV particles and for mPyV VP1 pentamers in complex with ganglioside receptor fragments (Stehle et al., 1994; Stehle & Harrison, 1997) as well as for the SV40 VP1 pentamer in complex with GM1 (Neu et al., 2008). The glycan-binding properties of the human polyomaviruses are currently being investigated.
The available structures show that VP1 forms a scaffold that can modulate the specificity of interaction through small changes in surface loops. We plan to generate a set of perhaps five different structures that highlight conserved as well as non-conserved interactions with different gangliosides, thereby providing a platform for understanding and altering receptor-binding properties. This work is important, as there are few known examples of viral proteins from non-enveloped viruses with a common fold for which subtle modulations of surface properties result in altered glycan-binding specificities.
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CFG Participating Investigators contributing to the understanding of this paradigm
CFG Participating Investigators (PIs) contributing to the understanding of VP1 include: Niklas Arnberg, Ten Feizi, Thilo Stehle
Progress toward understanding this GBP paradigm
Carbohydrate ligands
Cellular expression
Structure
Biological roles of GBP-ligand interaction
CFG resources used in investigations
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for "polyoma".
Glycan profiling
Glycogene microarray
Knockout mouse lines
Glycan array
The CFG glycan array was used to determine the ligand specificity for SV40. This information was then used to crystallize SV40 VP1 in complex with the oligosaccharide portion of the GM1 gangloside.
Related GBPs
Functionally (but not structurally) related are the pentameric B proteins of the AB5-type toxins, such as Subtilase cytotoxin (SubAB). These also interact with gangliosides.
References
Acknowledgements
The CFG is grateful to the following PIs for their contributions to this wiki page: Mavis McKenna, Thilo Stehle
