4leb
From Proteopedia
Structure of the Als3 adhesin from Candida albicans, residues 1-299 (mature sequence) in complex with hepta-threonine
Structural highlights
Function[ALS3_CANAX] Cell surface adhesion protein which mediates both yeast-to-host tissue adherence and yeast aggregation. Plays an important role in the pathogenesis of C.albicans infections. Necessary for C.albicans to bind to N-cadherin on endothelial cells and E-cadherin on oral epithelial cells and subsequent endocytosis by these cells (By similarity). Publication Abstract from PubMedThe 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 assess 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. PBC-mutant phenotype was evaluated in assays using monolayers of human pharyngeal epithelial (FaDu) and umbilical vein endothelial (HUVEC) cells, and freshly collected human buccal epithelial cells (BEC) in suspension. Loss of PBC function resulted in an adhesion phenotype that was indistinguishable from the deltaals3/deltaals3 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. The Peptide-Binding Cavity is Essential for Als3-mediated Adhesion of Candida albicans to Human Cells.,Lin J, Oh SH, Jones R, Garnett JA, Salgado PS, Rusnakova S, Matthews S, Hoyer LL, Cota E J Biol Chem. 2014 May 6. pii: jbc.M114.547877. PMID:24802757[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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