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|Title:||Structural basis for promiscuity and specificity during Candida glabrata invasion of host epithelia||Authors:||Maestre-Reyna, M.
Veelders, M. S.
|Keywords:||DRNTU::Science::Biological sciences||Issue Date:||2012||Source:||Maestre-Reyna, M., Diderrich, R., Veelders, M. S., Eulenburg, G., Kalugin, V., Brückner, S., et al. (2012). Structural basis for promiscuity and specificity during Candida glabrata invasion of host epithelia. Proceedings of the National Academy of Sciences, 109(42), 16864-16869.||Series/Report no.:||Proceedings of the national academy of sciences||Abstract:||The human pathogenic yeast Candida glabrata harbors more than 20 surface-exposed, epithelial adhesins (Epas) for host cell adhesion. The Epa family recognizes host glycans and discriminates between target tissues by their adhesin (A) domains, but a detailed structural basis for ligand-binding specificity of Epa proteins has been lacking so far. In this study, we provide high-resolution crystal structures of the Epa1A domain in complex with different carbohydrate ligands that reveal how host cell mucin-type O-glycans are recognized and allow a structure-guided classification of the Epa family into specific subtypes. Further detailed structural and functional characterization of subtype-switched Epa1 variants shows that specificity is governed by two inner loops, CBL1 and CBL2, involved in calcium binding as well as by three outer loops, L1, L2, and L3. In summary, our study provides the structural basis for promiscuity and specificity of Epa adhesins, which might further contribute to developing anti-adhesive antimycotics and combating Candida colonization.||URI:||https://hdl.handle.net/10356/97909
|DOI:||10.1073/pnas.1207653109||Rights:||© 2012 National Academy of Sciences. This paper was published in Proceedings of the National Academy of Sciences and is made available as an electronic reprint (preprint) with permission of National Academy of Sciences. The paper can be found at the following official DOI: [http://dx.doi.org/10.1073/pnas.1207653109]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Journal Articles|
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