Document Detail

Structural basis for promiscuity and specificity during Candida glabrata invasion of host epithelia.
MedLine Citation:
PMID:  23035251     Owner:  NLM     Status:  MEDLINE    
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.
Manuel Maestre-Reyna; Rike Diderrich; Maik Stefan Veelders; Georg Eulenburg; Vitali Kalugin; Stefan Brückner; Petra Keller; Steffen Rupp; Hans-Ulrich Mösch; Lars-Oliver Essen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-03
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-17     Completed Date:  2012-12-31     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  16864-9     Citation Subset:  IM    
Biomedical Research Center/Department of Chemistry, Philipps-Universität Marburg, D-35032 Marburg, Germany.
Data Bank Information
Bank Name/Acc. No.:
PDB/4AF9;  4AFA;  4AFB;  4AFC;  4ASL
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MeSH Terms
Calcium / metabolism
Candida glabrata / chemistry*,  physiology
Cluster Analysis
Computational Biology
Crystallography, X-Ray
Fungal Proteins / chemistry*,  genetics
Lectins / chemistry*,  genetics
Models, Molecular*
Multigene Family / genetics*
Protein Binding
Protein Conformation*
Reg. No./Substance:
0/Fungal Proteins; 0/Lectins; 0/Polysaccharides; 0/epithelial adhesin 1, Candida glabrata; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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