View source for Polyomavirus capsid protein (VP1)

'''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<ref>Feng H, Shuda M, Chang Y, Moore PS: Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008, 319:1096-1100.</ref>. All polyomavirus capsids are constructed from 360 copies of the major coat protein, VP1, arranged in pentamers on a T=7 icosahedral lattice<ref>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.</ref>. 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<ref>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.</ref><ref>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.</ref>. Crystal structures are available for complete mPyV particles and for mPyV VP1 pentamers in complex with ganglioside receptor fragments<ref>Stehle T, Yan Y, Benjamin TL, Harrison SC: Structure of murine polyomavirus complexed with an oligosaccharide receptor fragment. Nature 1994, 369:160-163.</ref><ref>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.</ref> as well as for the SV40 VP1 pentamer in complex with GM1<ref>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.</ref>. 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.

== 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 ===

<br>
=== Cellular expression of GBP and ligands ===

<br>
=== Biosynthesis of ligands ===

<br>
=== Structure ===

<br>
=== Biological roles of GBP-ligand interaction ===

<br>
== 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 [http://www.functionalglycomics.org/glycomics/search/jsp/landing.jsp?query=polyoma&maxresults=20 CFG database search results for "polyoma"].

=== Glycan profiling ===

<br>
=== Glycogene microarray ===

<br>
=== Knockout mouse lines ===

<br>
=== 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. 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 ==
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 ==
<references/>

== Acknowledgements ==
The CFG is grateful to the following PIs for their contributions to this wiki page: Mavis McKenna, Thilo Stehle