title: Structural Hot Spots Determine Functional Diversity of the Candida glabrata Epithelial Adhesin Family.
abstract: For host colonization, the human fungal pathogen Candida glabrata is known to utilize a large family of highly related surface-exposed cell wall proteins, the lectin-like epithelial adhesins (Epas). To reveal the structure-function relationships within the entire Epa family, we have performed a large scale functional analysis of the adhesion (A) domains of 17 Epa paralogs in combination with three-dimensional structural studies of selected members with cognate ligands. Our study shows that most EpaA domains exert lectin-like functions and together recognize a wide variety of glycans with terminal galactosides for conferring epithelial cell adhesion. We further identify several conserved and variable structural features within the diverse Epa ligand binding pockets, which affect affinity and specificity. These features rationalize why mere phylogenetic relationships within the Epa family are weak indicators for functional classification and explain how Epa-like adhesins have evolved in C. glabrata and related fungal species.
authors.affiliation: From the Departments of Genetics and.
authors.forename: Rike
authors.initials: R
authors.lastname: Diderrich
authors.affiliation: Biochemistry, Philipps-Universität, 35043 Marburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kock
authors.affiliation: Biochemistry, Philipps-Universität, 35043 Marburg, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Maestre-Reyna
authors.affiliation: the Fraunhofer-Institut für Grenzflächen und Bioverfahrenstechnik, 70569 Stuttgart, Germany, and.
authors.forename: Petra
authors.initials: P
authors.lastname: Keller
authors.affiliation: Biochemistry, Philipps-Universität, 35043 Marburg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Steuber
authors.affiliation: the Fraunhofer-Institut für Grenzflächen und Bioverfahrenstechnik, 70569 Stuttgart, Germany, and the Institut für Grenzflächenverfahrenstechnik und Plasmatechnologie, Universität Stuttgart, 70569 Stuttgart, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Rupp
authors.affiliation: Biochemistry, Philipps-Universität, 35043 Marburg, Germany, essen@chemie.uni-marburg.de.
authors.forename: Lars-Oliver
authors.initials: LO
authors.lastname: Essen
authors.affiliation: From the Departments of Genetics and moesch@staff.uni-marburg.de.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Mösch
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D005075:Biological Evolution; D041221:Candida glabrata / Q000737:chemistry* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D014644:Genetic Variation; D037102:Lectins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D015815:Cell Adhesion Molecules; D005656:Fungal Proteins; D037102:Lectins; D011134:Polysaccharides; D011994:Recombinant Proteins
keywords: Candida glabrata; PA14 domain; cell adhesion; cell surface; epithelial adhesin; host-pathogen interaction; lectin; structure-function; yeast