Difference between revisions of "CBM47"
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=== Carbohydrate ligands === | === Carbohydrate ligands === | ||
| − | CBM47 is a fucose specific binding module that is related to ''Anguilla anguilla'' fucolectin. The high affinity ligand for CBM47 has been determined from glycan microarray screening on the CFG microarray to be Fucα1-2Galβ1-4(Fucα1-3)GlcNAc [Lewis <sup>y</sup>]<ref name="Boraston 2006"/>. | + | CBM47 is a fucose specific binding module that is related to ''Anguilla anguilla'' fucolectin. The high affinity ligand for CBM47 has been determined from glycan microarray screening on the CFG microarray[http://www.functionalglycomics.org/glycomics/HServlet?operation=view&sideMenu=no&psId=primscreen_GLYCAN_v3_34_08192004#]to be Fucα1-2Galβ1-4(Fucα1-3)GlcNAc [Lewis <sup>y</sup>]<ref name="Boraston 2006"/>. |
[[File:Lewisy.jpg]] | [[File:Lewisy.jpg]] | ||
Revision as of 22:31, 28 June 2010
Enzymes that degrade host glycans are increasingly being found as virulence factors in pathogenic bacteria[1][2]. A common property of extracellular glycan degrading enzymes found in such bacteria is multi-modularity; these enzymes often comprise a large number of modules with a variety of functions. The most common class of ancillary module are carbohydrate-binding modules (CBMs)[3], which are alternatively referred to as lectin-domains. These modules are responsible for targeting carbohydrate-degrading enzymes to a glycan substrate or, when the enzymes are attached to the bacterial cell-surface, likely also function to adhere the bacterium to a glycan[4]. The presence of these lectin-domains in multi-modular proteins and their contribution of glycan binding function to catalytically active proteins distinguishes these modules from other bacterial glycan-binding proteins (GBPs). The CBM47 modules from the Streptococcus pneumoniae enzyme SpGH98 (or "fucolectin-related protein") are specific to the Lewisy antigen[5], which is quite rare among all GBPs, and function to target this enzyme to this antigen when present on epithelial cells[6]. Recognition and destruction of this antigen appears to be a critical process in pneumococcal virulence[2][7].
CFG Participating Investigators contributing to the understanding of this paradigm
This is a very new area of investigation. CFG Participating Investigators (PIs) that have screened other CBMs or proteins containing CBMs include: Alisdair Boraston, Garry Taylor, Warren Wakarchuck
Progress toward understanding this GBP paradigm
Carbohydrate ligands
CBM47 is a fucose specific binding module that is related to Anguilla anguilla fucolectin. The high affinity ligand for CBM47 has been determined from glycan microarray screening on the CFG microarray[1]to be Fucα1-2Galβ1-4(Fucα1-3)GlcNAc [Lewis y][5].
Cellular expression of GBP and ligands
Biosynthesis of ligands
Structure
CBM47 originates from a multimodular S. pneumoniae that has an N-terminal, Lewisy degrading catalytic module. Indeed, three CBM47 modules are found in tandem.
The high resolution X-ray structures of the N-terminal and C-terminal CBM47 modules have been determined and the N-terminal module in complex with the Lewisy tetrasaccharide[5].
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 CBM.
Glycan profiling
Glycogene microarray
Knockout mouse lines
Glycan array
The specificity of several CBMs have been investigated by CFG glycan array analysis (example). Isolated glycans for structural and quantitative binding studies have also been obtained from the CFG.
Related GBPs
References
- ↑ Shelburne, S. A., Davenport, M. T., Keith, D. B. & Musser, J. M. (2008). The role of complex carbohydrate catabolism in the pathogenesis of invasive streptococci. Trends Microbiol 16, 318-25.
- ↑ 2.0 2.1 Hava, D. L. & Camilli, A. (2002). Large-scale identification of serotype 4 Streptococcus pneumoniae virulence factors. Mol Microbiol 45, 1389-406.
- ↑ Boraston, A. B., Bolam, D. N., Gilbert, H. J. & Davies, G. J. (2004). Carbohydrate-binding modules: fine tuning polysaccharide recognition. Biochem J 382, 769-782.
- ↑ Ficko-Blean, E., Gregg, K. J., Adams, J. J., Hehemann, J. H., Czjzek, M., Smith, S. P. & Boraston, A. B. (2009). Portrait of an enzyme, a complete structural analysis of a multimodular {beta}-N-acetylglucosaminidase from Clostridium perfringens. J Biol Chem 284, 9876-84.
- ↑ 5.0 5.1 5.2 Boraston, A. B., Wang, D. & Burke, R. D. (2006). Blood group antigen recognition by a Streptococcus pneumoniae virulence factor. J Biol Chem 281, 35263-35271.
- ↑ Higgins, M. A., Whitworth, G. E., El Warry, N., Randriantsoa, M., Samain, E., Burke, R. D., Vocadlo, D. J. & Boraston, A. B. (2009). Differential recognition and hydrolysis of host carbohydrate antigens by Streptococcus pneumoniae family 98 glycoside hydrolases. J Biol Chem 284, 26161-73.
- ↑ Embry, A., Hinojosa, E. & Orihuela, C. J. (2007). Regions of Diversity 8, 9 and 13 contribute to Streptococcus pneumoniae virulence. BMC Microbiol 7, 80.
Acknowledgements
The CFG is grateful to the following PIs for their contributions to this wiki page: Alisdair Boraston, Anne Imberty
