4AFC

Crystal Structure of subtype-switched Epithelial Adhesin 1 to 6 A domain (Epa1to6A) from Candida glabrata in complex with Galb1-3Glc

4AFC の概要

• エントリーDOI: 10.2210/pdb4afc/pdb
• 関連するPDBエントリー: 4A3X 4AF9 4AFA 4AFB 4ASL
• 分子名称: EPA1P, beta-D-galactopyranose-(1-3)-alpha-D-glucopyranose, CALCIUM ION, ... (6 entities in total)
• 機能のキーワード: cell adhesion, lectin, tissue invasion, pathogenicity
• 由来する生物種: CANDIDA GLABRATA
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29770.88

構造登録者

Maestre-Reyna, M.,Diderrich, R.,Veelders, M.S.,Eulenburg, G.,Kalugin, V.,Brueckner, S.,Keller, P.,Rupp, S.,Moesch, H.-U.,Essen, L.-O. (登録日: 2012-01-18, 公開日: 2012-10-17, 最終更新日: 2024-11-13)

主引用文献

Maestre-Reyna, M.,Diderrich, R.,Veelders, M.S.,Eulenburg, G.,Kalugin, V.,Bruckner, S.,Keller, P.,Rupp, S.,Mosch, H.,Essen, L.
Structural Basis for Promiscuity and Specificity During Candida Glabrata Invasion of Host Epithelia.
Proc.Natl.Acad.Sci.USA, 109:16864-, 2012

PubMed 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.

PubMed: 23035251
DOI: 10.1073/PNAS.1207653109

実験手法

X-RAY DIFFRACTION (1.55 Å)