A “dock, lock, and latch” Structural Model for a Staphylococcal Adhesin Binding to Fibrinogen

Gram-positive pathogens such as staphylococci contain multiple cell wall-anchored proteins that serve as an interface between the microbe and its environment. Some of these proteins act as adhesins and mediate bacterial attachment to host tissues. SdrG is a cell wall-anchored adhesin from Staphyloco...

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Bibliographic Details
Published in:Cell 2003-10, Vol.115 (2), p.217-228
Main Authors: Ponnuraj, Karthe, Bowden, M.Gabriela, Davis, Stacey, Gurusiddappa, S., Moore, Dwight, Choe, Damon, Xu, Yi, Hook, Magnus, Narayana, Sthanam V.L.
Format: Article
Language:English
Subjects:
Adhesins, Bacterial - chemistry
Adhesins, Bacterial - genetics
Adhesins, Bacterial - metabolism
Alanine - metabolism
Amino Acid Motifs
Amino Acid Sequence
Amino Acid Substitution
Bacterial Adhesion
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Binding Sites
Conserved Sequence
Crystallography, X-Ray
Fibrinogen - chemistry
Fibrinogen - drug effects
Fibrinogen - metabolism
Humans
Ligands
Models, Molecular
Molecular Sequence Data
Mutagenesis, Site-Directed
Peptides - chemistry
Peptides - genetics
Protein Binding
Protein Structure, Tertiary
SdrG protein
Serine - metabolism
Staphylococcus epidermidis
Staphylococcus epidermidis - metabolism
synthetic peptides
Thrombin - pharmacology
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Summary:Gram-positive pathogens such as staphylococci contain multiple cell wall-anchored proteins that serve as an interface between the microbe and its environment. Some of these proteins act as adhesins and mediate bacterial attachment to host tissues. SdrG is a cell wall-anchored adhesin from Staphylococcus epidermidis that binds to the Bβ chain of human fibrinogen (Fg) and is necessary and sufficient for bacterial attachment to Fg-coated biomaterials. Here, we present the crystal structures of the ligand binding region of SdrG as an apoprotein and in complex with a synthetic peptide analogous to its binding site in Fg. Analysis of the crystal structures, along with mutational studies of both the protein and of the peptide, reveals that SdrG binds to its ligand with a dynamic “dock, lock, and latch” mechanism. We propose that this mechanism represents a general mode of ligand binding for structurally related cell wall-anchored proteins of gram-positive bacteria.
ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(03)00809-2