Structural Basis for the broad tissue tropism of the pathogenic fungus Candida Albicans

DOI: 10.1073/pnas.1103496108
PMID: 21896717

Authors: Paula S. Salgado (Imperial College London) , Robert Yan (Imperial College London) , Jonathan D. Taylor (Imperial College London) , Lynne Buchnell (Imperial College) , Rhian Jones (Imperial College London) , Lois L. Hoyer (Imperial College London) , Steve Matthews (Imperial College London) , Peter Simpson (Imperial College London) , Ernesto Cota-segura (Imperial College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences

State: Published (Approved)
Published: September 2011
Diamond Proposal Number(s): 1227

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.

Journal Keywords: Candida; Candidiasis; Cross; Fungal; Host-Pathogen; Humans; Ligands; Magnetic; Models; Molecular; Mutation; Protein; Tertiary; Scattering; Small; Sequence; Amino; X-Ray Diffraction

Subject Areas: Medicine, Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography