The epithelial adhesin 1 (Epa1p) from the human-pathogenic yeast Candida glabrata: structural and functional study of the carbohydrate-binding domain

Acta Crystallographica. Section D, Biological Crystallography
Francesco S IelasiRonnie G Willaert

Abstract

The yeast Candida glabrata represents the second major cause of clinical candidiasis cases in the world. The ability of this opportunistic pathogen to adhere to human epithelial and endothelial cells relies on the Epa adhesins, a large set of cell-wall proteins whose N-terminal domains are endowed with a calcium-dependent lectin activity. This feature allows the yeast cells to adhere to host cells by establishing multiple interactions with the glycans expressed on their cell membrane. The ligand-binding domain of the Epa1p adhesin, which is one of the best characterized in the Epa family, was expressed in Escherichia coli, purified and crystallized in complex with lactose. Sequence identity with the domain of another yeast adhesin, the Flo5p flocculin from Saccharomyces cerevisiae, was exploited for molecular replacement and the structure of the domain was solved at a resolution of 1.65 Å. The protein is a member of the PA14 superfamily. It has a β-sandwich core and a DcisD calcium-binding motif, which is also present in the binding site of Flo5p. However, Epa1p differs from this homologue by the lack of a Flo5-like subdomain and by a significantly decreased accessibility of the solvent to the binding site, in which a calcium i...Continue Reading

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Citations

Oct 5, 2012·Proceedings of the National Academy of Sciences of the United States of America·Manuel Maestre-ReynaLars-Oliver Essen
Feb 12, 2013·Eukaryotic Cell·Piet W J de GrootNeeraj Chauhan
Sep 17, 2013·BMC Genomics·Toni GabaldónCécile Fairhead
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Jul 9, 2013·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Francesco S IelasiRonnie G Willaert
Nov 12, 2016·Biochemical and Biophysical Research Communications·Gabriela Pérez-FloresPatricia Pérez-Cornejo
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Jun 25, 2015·The Journal of Biological Chemistry·Rike DiderrichHans-Ulrich Mösch
Oct 31, 2018·Journal of Fungi·Ronnie G Willaert
Mar 11, 2017·Proceedings of the National Academy of Sciences of the United States of America·Pawel Dabrowski-Tumanski, Joanna I Sulkowska
Nov 15, 2018·Frontiers in Microbiology·Michael KockLars-Oliver Essen
May 23, 2018·Journal of Fungi·Bea TimmermansPatrick Van Dijck
Oct 10, 2020·Biological Chemistry·Lars-Oliver EssenHans-Ulrich Mösch
Jun 8, 2021·RSC Medicinal Chemistry·Harlei MartinTrinidad Velasco-Torrijos

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