4LEB

Structure of the Als3 adhesin from Candida albicans, residues 1-299 (mature sequence) in complex with hepta-threonine

4LEB の概要

• エントリーDOI: 10.2210/pdb4leb/pdb
• 関連するPDBエントリー: 4LE8 4LEE
• 分子名称: Agglutinin-like protein 3, hepta-threonine (3 entities in total)
• 機能のキーワード: adhesin, peptide binding protein, biofilm formation, cellular adhesion, peptides, cell surface, cell adhesion
• 由来する生物種: Candida albicans (Yeast); 詳細
• 細胞内の位置: Cell membrane (By similarity); Lipid-anchor, GPI-anchor (By similarity): O74623
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 33121.59

構造登録者

Lin, J.,Garnett, J.A.,Cota, E. (登録日: 2013-06-25, 公開日: 2014-05-14, 最終更新日: 2024-11-06)

主引用文献

Lin, J.,Oh, S.H.,Jones, R.,Garnett, J.A.,Salgado, P.S.,Rusnakova, S.,Matthews, S.J.,Hoyer, L.L.,Cota, E.
The Peptide-binding Cavity Is Essential for Als3-mediated Adhesion of Candida albicans to Human Cells.
J.Biol.Chem., 289:18401-18412, 2014

PubMed Abstract: The adhesive phenotype of Candida albicans contributes to its ability to colonize the host and cause disease. Als proteins are one of the most widely studied C. albicans virulence attributes; deletion of ALS3 produces the greatest reduction in adhesive function. Although adhesive activity is thought to reside within the N-terminal domain of Als proteins (NT-Als), the molecular mechanism of adhesion remains unclear. We designed mutations in NT-Als3 that test the contribution of the peptide-binding cavity (PBC) to C. albicans adhesion and assessed the adhesive properties of other NT-Als3 features in the absence of a functional PBC. Structural analysis of purified loss-of-PBC-function mutant proteins showed that the mutations did not alter the overall structure or surface properties of NT-Als3. The mutations were incorporated into full-length ALS3 and integrated into the ALS3 locus of a deletion mutant, under control of the native ALS3 promoter. The PBC mutant phenotype was evaluated in assays using monolayers of human pharyngeal epithelial and umbilical vein endothelial cells, and freshly collected human buccal epithelial cells in suspension. Loss of PBC function resulted in an adhesion phenotype that was indistinguishable from the Δals3/Δals3 strain. The adhesive contribution of the Als3 amyloid-forming-region (AFR) was also tested using these methods. C. albicans strains producing cell surface Als3 in which the amyloidogenic potential was destroyed showed little contribution of the AFR to adhesion, instead suggesting an aggregative function for the AFR. Collectively, these results demonstrate the essential and principal role of the PBC in Als3 adhesion.

PubMed: 24802757
DOI: 10.1074/jbc.M114.547877

実験手法

X-RAY DIFFRACTION (1.4 Å)