The N‐terminal part of Als1 protein from Candida albicans specifically binds fucose‐containing glycans

Abstract

SummaryThe opportunistic pathogen Candida albicans expresses on its surface Als (Agglutinin like sequence) proteins, which play an important role in the adhesion to host cells and in the development of candidiasis. The binding specificity of these proteins is broad, as they can bind to various mammalian proteins, such as extracellular matrix proteins, and N-and E-cadherins. The N-terminal part of Als proteins constitutes the substrate-specific binding domain and is responsible for attachment to epithelial and endothelial cells. We have used glycan array screening to identify possible glycan receptors for the binding domain of Als1p-N. Under those conditions, Als1p-N binds specifically to fucose-containing glycans, which adds a lectin function to the functional diversity of the Als1 protein. The binding between Als1p-N and BSAfucose glycoconjugate was quantitatively characterized using surface plasmon resonance, which demonstrated a weak millimolar affinity between Als1p-N and fucose. Furthermore, we have also quantified the affinity of Als1p-N to the extracellular matrix proteins proteins fibronectin and laminin, which is situated in the micromolar range. Surface plasmon resonance characterization of Als1p-N-Als1p-N interaction was in the micromolar affinity range.

Adhesins in Human Fungal Pathogens: Glue with Plenty of Stick

“…This is consistent with results from earlier studies showing that Als proteins bind to a number of structurally unrelated proteins and peptides from randomly generated sequences (51). In addition, the N-terminal part of Als1 protein specifically binds fucose-containing glycans (39). Adhesion through Als proteins can be activated and increased dramatically by amyloid nanodomain formation (see section below).…”

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

“…More recently it has been shown that a fragment encompassing residues 18-432 of Als1 recognizes different fucose-containing sugars from a glycan array (28). The authors also demonstrate that the interaction of this fragment with a glycoconjugate of fucose and BSA has a dissociation constant in the submillimolar range (K D ¼ 210 μM), which opens the possibility that Als proteins can specifically recognize fucose-related glycans or glycoproteins in the peptide-binding cavity or an alternative binding site.…”

Strengthening relationships: amyloids create adhesion nanodomains in yeasts

“…Als proteins bind to other Als proteins, as well as to non-related proteins on the surfaces of other yeasts and bacteria to form aggregates and co-aggregates, and may well be a factor in the high level of co-infection of C. albicans with other yeasts and bacteria [30, 33-37]. At least one Als protein can also bind to fucose-containing glycans, a finding that further expands the range of potential ligands in host tissues [27]. The peptide and glycan interactions have K d values near 10 -4 -10 -3 M, with rapid dissociation rates [27].…”