Structural basis for promiscuity and specificity during Candida glabrata invasion of host epithelia
Open accessAbstract
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.
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Epa1, Epa6 and Epa7 show glycan ligand specificity, with Epa6 having the widest substrate specificity.
“Despite the preference for the terminal galactose, Epa1, 6 and 7 showed glycan ligand specificity, with Epa6 having the widest substrate specificity [35,43].”
From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [43]
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- Authors
- Maestre-Reyna, M., Diderrich, R., Veelders, M. S., Eulenburg, G., Kalugin, V., Brückner, S., Keller, P., Rupp, S., Mösch, H.-U., & Essen, L.-O.
- Affiliations
- Biomedical Research Center/Department of Chemistry, Philipps-Universität Marburg, D-35032 Marburg, Germany;
- Philipps University of Marburg (DE)
- Fraunhofer Institute for Interfacial Engineering and Biotechnology (DE)
- Corresponding author
- Essen, Lars-Oliver
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-10-03
- Volume
- 109
- Issue
- 42
- Pages
- 16864-16869
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3479469
- OpenAlex
- W2150187215
- Cited by
- 67
- References
- 29
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 9 · 2020: 7 · 2019: 5 · 2018: 7 · 2017: 4 · 2016: 7 · 2015: 6 · 2014: 5 · 2013: 9
- FWCI
- 4.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DR-NTU (Nanyang Technological University) (submittedVersion)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (GRK1216)
- European Synchrotron Radiation Facility
- Zentrum für Synthetische Mikrobiologie
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Keywords
- Candida glabrata, mucin-type O-glycans, host cell adhesion, ligand specificity, crystal structure, calcium-binding loop, fungal colonization
- MeSH terms
- Calcium, Fluorescence, Fungal Proteins, Multigene Family, Models, Molecular, Phylogeny, Polysaccharides, Protein Binding, Protein Conformation, Cluster Analysis, Crystallography, X-Ray, Computational Biology, Lectins, Candida glabrata
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