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.

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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