Saima's Research Blog
Molecular Recognition of Cell Adhesion Proteins: How Do Salt Bridge Interactions Influence a Pathogen-Host Complex?
An estimated 70% of people are infected with the fungal pathogen Candida. Though usually commensal, the species promotes nosocomial infections and can be life-threatening for those with weakened immune systems. Many pathogenic microorganisms express cell adhesion proteins on their surfaces which they use to stick to host tissues, such as our skin, to cause infection. Candida albicans expresses several kinds of agglutinin-like (Als) adhesin protein domains, which have the remarkable properties of being able to bind to a wide variety of peptide and protein substrates on a host cell surface. Typically, these proteins bind to the C-terminus of their substrates. The X-ray structure of Candida albicans ALS9-2 with human fibrinogen gamma peptide reveals a key salt bridge between the negatively charged C-terminus of the peptide and Lys59 located at the bottom of the binding cavity. Experiments show that this salt bridge must form in order for a substrate to bind to the adhesion protein, however there are limited structural details about how the salt bridge stabilizes this peptide in the binding cavity. The goal of this work is to determine how this salt bridge influences the molecular recognition of cell adhesion proteins to their host cells. We investigated this question by performing all-atom molecular dynamics simulations of the ALS-9-2 protein-peptide complex with a negatively charged and neutral C-terminus on the peptide and monitored the stability of the complex to assess the importance of this salt bridge interaction.