Understanding the Structural Basis for Functional Differences in Staphylococcal MSCRAMMS SDRE1 and BBP/SDRE2 and Their Role in Species Tropism
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Date
2015-04-29
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Abstract
Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs) on Staphylococcus aureus play roles in attachment, invasion and immune evasion. It has been previously reported that bone sialoprotein-binding protein (Bbp) binds to human fibrinogen. Herein, we show that Bbp and SD-repeat protein E (SdrE) are allelic variants whose in vitro fibrinogen binding profile provides a rationale for the epidemiological presence of Bbp and SdrE in human and animal Staphylococcal strains. Epidemiological studies show that bbp is found in 32% of human staphylococcal strains, whereas it is nearly absent from animal staphylococcal strains. We show through basic and advanced in vitro biochemical techniques that Bbp shows a vastly higher affinity for human fibrinogen than SdrE and that Bbp specifically displays affinity for fibrinogen from humans. In contrast, SdrE shows varying affinity for fibrinogen from a wide array of various animals.
The structural basis for this difference is elucidated by determining the molecular structures of Bbp and SdrE with no ligands as well as the molecular structures of Bbp and SdrE in complex with a peptide representing the fibrinogen ligand binding sequence. Data from these structural analyses were used to inform mutational analysis of the recombinant proteins, both to confirm the integrity structural models and to discover which residues are responsible for the differences in binding profile. From these data, we show that the Lock Regions of the two proteins are a major cause of this difference in binding profile and species tropism.
The structural basis for this difference is elucidated by determining the molecular structures of apo-Bbp and apo-SdrE as well as the molecular structure of Bbp in complex with a peptide representing the ligand binding sequence. Data from these structural analyses were used to inform mutational analysis of the recombinant proteins, both to confirm the integrity structural models and to discover which residues are responsible for the differences in binding profile. From these data, we show that the Lock Regions of the two proteins are a major cause of this difference in binding profile and species tropism.
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MRSA, MSCRAMM, species tropism