Polyomavirus capsid protein (VP1)
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| - | === Cellular expression === | + | === Cellular expression of GBP and ligands === |
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| + | === Biosynthesis of ligands === | ||
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=== Glycan array === | === Glycan array === | ||
| - | The CFG glycan array was used to determine the [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_405_07312006 ligand specificity for SV40]. This information was then used to crystallize SV40 VP1 in complex with the oligosaccharide portion of the GM1 gangloside. | + | The CFG glycan array was used to determine the [http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_PA_v2_405_07312006 ligand specificity for SV40]. This information was then used to crystallize SV40 VP1 in complex with the oligosaccharide portion of the GM1 gangloside. To see all glycan array results for VP1, click [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=VP1&cat=coreh here]. |
== Related GBPs == | == Related GBPs == | ||
Revision as of 22:53, 21 June 2010
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[1]. All polyomavirus capsids are constructed from 360 copies of the major coat protein, VP1, arranged in pentamers on a T=7 icosahedral lattice[2]. 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[3][4]. Crystal structures are available for complete mPyV particles and for mPyV VP1 pentamers in complex with ganglioside receptor fragments[5][6] as well as for the SV40 VP1 pentamer in complex with GM1[7]. 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.
Contents |
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 of GBP and ligands
Biosynthesis of ligands
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. To see all glycan array results for VP1, click here.
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
- ↑ Feng H, Shuda M, Chang Y, Moore PS: Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008, 319:1096-1100.
- ↑ Liddington RC, Yan Y, Moulai J, Sahli R, Benjamin TL, Harrison SC: Structure of simian virus 40 at 3.8-A resolution. Nature 1991, 354:278-284.
- ↑ Tsai B, Gilbert JM, Stehle T, Lencer W, Benjamin TL, Rapoport TA: Gangliosides are receptors for murine polyoma virus and SV40. Embo J 2003, 22:4346-4355.
- ↑ Low JA, Magnuson B, Tsai B, Imperiale MJ: Identification of gangliosides GD1b and GT1b as receptors for BK virus. J Virol 2006, 80:1361-1366.
- ↑ Stehle T, Yan Y, Benjamin TL, Harrison SC: Structure of murine polyomavirus complexed with an oligosaccharide receptor fragment. Nature 1994, 369:160-163.
- ↑ Stehle T, Harrison SC: High-resolution structure of a polyomavirus VP1-oligosaccharide complex: implications for assembly and receptor binding. The EMBO Journal 1997, 16:5139-5148.
- ↑ Neu U, Woellner K, Gauglitz G, Stehle T: Structural basis of GM1 ganglioside recognition by simian virus 40. Proc Natl Acad Sci U S A 2008, 105:5219-5224.
Acknowledgements
The CFG is grateful to the following PIs for their contributions to this wiki page: Mavis McKenna, Thilo Stehle
