title: Structural basis for the broad specificity to host-cell ligands by the pathogenic fungus Candida albicans.
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.
authors: Division of Molecular Biosciences, Imperial College London, Exhibition Road, South Kensington SW7 2AZ, United Kingdom.
authors: Paula S
authors: PS
authors: Salgado
authors: Robert
authors: R
authors: Yan
authors: Jonathan D
authors: JD
authors: Taylor
authors: Lynn
authors: L
authors: Burchell
authors: Rhian
authors: R
authors: Jones
authors: Lois L
authors: LL
authors: Hoyer
authors: Steve J
authors: SJ
authors: Matthews
authors: Peter J
authors: PJ
authors: Simpson
authors: Ernesto
authors: E
authors: Cota
mesh_terms: D000595:Amino Acid Sequence; D002176:Candida albicans / Q000378:metabolism / Q000502:physiology; D002177:Candidiasis / Q000378:metabolism / Q000382:microbiology; D003428:Cross Infection / Q000382:microbiology; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D053838:Scattering, Small Angle; D017386:Sequence Homology, Amino Acid; D014961:X-Ray Diffraction
chemical_list: D005656:Fungal Proteins; D008024:Ligands