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Updated: May 29, 2026

An Ex vivo Assay to Study Candida albicans Hyphal Morphogenesis in the Gastrointestinal Tract
Published on: July 1, 2020
Structural basis for the broad specificity to host-cell ligands by the pathogenic fungus Candida albicans
Paula S Salgado1, Robert Yan, Jonathan D Taylor
1Division 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.
Insights
Candida albicans uses agglutinin-like sequence (Als) proteins to bind host cells. Structural analysis reveals these adhesins recognize peptide ligands through a specific binding cavity, involving water molecules and a key lysine residue.
Area of Science:
- Microbiology
- Structural Biology
- Biochemistry
Background:
- Candida albicans is a prevalent human fungal pathogen causing serious infections.
- Agglutinin-like sequence (Als) glycoproteins are key virulence factors in C. albicans.
- Als proteins mediate host cell adhesion, biofilm formation, and amyloid fiber assembly.
Purpose of the Study:
- To elucidate the high-resolution structure of N-terminal Als adhesins (NT-Als).
- To understand the molecular mechanism of ligand recognition by NT-Als.
- To characterize NT-Als as a novel class of peptide-binding proteins.
Main Methods:
- High-resolution structural determination of N-terminal Als adhesins (NT-Als).
- Analysis of protein-ligand interactions within the NT-Als binding cavity.
- Identification of key residues and water molecules involved in ligand binding.
Main Results:
- NT-Als possess a unique binding motif for flexible C-terminal peptides in extended conformations.
- An invariant lysine residue is crucial for recognizing the ligand's C-terminal carboxylate.
- A network of water molecules facilitates the recognition of diverse peptide sequences.
Conclusions:
- NT-Als adhesins represent a distinct family of peptide-binding proteins.
- This mechanism reveals an unexpected adhesion system for C. albicans.
- The findings highlight a primary mechanism for protein-protein interactions at the Candida/host-cell interface.
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