Open Accessβ-Neurexin Is a Ligand for the Staphylococcus aureus MSCRAMM SdrC
Author(s) -
E. Magda Barbu,
Vannakambadi K. Ganesh,
Shivasankarappa Gurusiddappa,
Ross MacKenzie,
Timothy J. Foster,
Thomas C. Südhof,
Magnus Höök
Publication year - 2010
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1000726
Subject(s) - subfamily , ligand (biochemistry) , biology , peptide sequence , bacteria , peptide , recombinant dna , staphylococcus aureus , microbiology and biotechnology , chemistry , biochemistry , receptor , genetics , gene
Gram-positive bacteria contain a family of surface proteins that are covalently anchored to the cell wall of the organism. These cell-wall anchored (CWA) proteins appear to play key roles in the interactions between pathogenic organisms and the host. A subfamily of the CWA has a common structural organization with multiple domains adopting characteristic IgG-like folds. The identified m icrobial s urface c omponents r ecognizing a dhesive m atrix m olecules (MSCRAMMs) belong to this subfamily, as does SdrC from S. aureus . However, an interactive host ligand for the putative MSCRAMM SdrC was not previously identified. We have screened a phage display peptide library and identified a peptide sequence found in β-neurexin that binds SdrC. A synthetic peptide corresponding to the identified sequence as well as a recombinant form of the β-neurexin 1 exodomain binds SdrC with high affinity and specificity. Furthermore, expression of SdrC on bacteria greatly enhances microbial adherence to cultured mammalian cells expressing β-neurexin on their surface. Taken together, our experimental results demonstrate that β-neurexin is a ligand for SdrC. This interaction involves a specific sequence located in the N-terminal region of the mammalian protein and the N 2 N 3 domain of the MSCRAMM. The fact that these two proteins interact when expressed on the appropriate cells demonstrates the functionality of the interaction. Possible implications of this interaction are discussed.