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Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):15775-9. doi: 10.1073/pnas.1103496108. Epub 2011 Sep 6.

Structural basis for the broad specificity to host-cell ligands by the pathogenic fungus Candida albicans.

Author information

1
Division of Molecular Biosciences, Imperial College London, Exhibition Road, South Kensington SW7 2AZ, United Kingdom.

Abstract

Candida albicans is the most prevalent fungal pathogen in humans and a major source of life-threatening nosocomial infections. The Als (agglutinin-like sequence) glycoproteins are an important virulence factor for this fungus and have been associated with binding of host-cell surface proteins and small peptides of random sequence, the formation of biofilms and amyloid fibers. High-resolution structures of N-terminal Als adhesins (NT-Als; up to 314 amino acids) show that ligand recognition relies on a motif capable of binding flexible C termini of peptides in extended conformation. Central to this mechanism is an invariant lysine that recognizes the C-terminal carboxylate of ligands at the end of a deep-binding cavity. In addition to several protein-peptide interactions, a network of water molecules runs parallel to one side of the ligand and contributes to the recognition of diverse peptide sequences. These data establish NT-Als adhesins as a separate family of peptide-binding proteins and an unexpected adhesion system for primary, widespread protein-protein interactions at the Candida/host-cell interface.

PMID:
21896717
PMCID:
PMC3179088
DOI:
10.1073/pnas.1103496108
[Indexed for MEDLINE]
Free PMC Article

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