Crystal structures of Bbp from Staphylococcus aureus reveal the ligand binding mechanism with Fibrinogen α
Protein & Cell
; (12): 757-766, 2015.
Article
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| ID: wpr-757190
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WPRO
ABSTRACT
Bone sialoprotein-binding protein (Bbp), a MSCRAMMs (Microbial Surface Components Recognizing Adhesive Matrix Molecules) family protein expressed on the surface of Staphylococcus aureus (S. aureus), mediates adherence to fibrinogen α (Fg α), a component in the extracellular matrix of the host cell and is important for infection and pathogenesis. In this study, we solved the crystal structures of apo-Bbp(273-598) and Bbp(273-598)-Fg α(561-575) complex at a resolution of 2.03 Å and 1.45 Å, respectively. Apo-Bbp(273-598) contained the ligand binding region N2 and N3 domains, both of which followed a DE variant IgG fold characterized by an additional D1 strand in N2 domain and D1' and D2' strands in N3 domain. The peptide mapped to the Fg α(561-575) bond to Bbp(273-598) on the open groove between the N2 and N3 domains. Strikingly, the disordered C-terminus in the apo-form reorganized into a highly-ordered loop and a β-strand G'' covering the ligand upon ligand binding. Bbp(Ala298-Gly301) in the N2 domain of the Bbp(273-598)-Fg α(561-575) complex, which is a loop in the apo-form, formed a short α-helix to interact tightly with the peptide. In addition, Bbp(Ser547-Gln561) in the N3 domain moved toward the binding groove to make contact directly with the peptide, while Bbp(Asp338-Gly355) and Bbp(Thr365-Tyr387) in N2 domain shifted their configurations to stabilize the reorganized C-terminus mainly through strong hydrogen bonds. Altogether, our results revealed the molecular basis for Bbp-ligand interaction and advanced our understanding of S. aureus infection process.
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Texto completo:
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Índice:
WPRIM
Asunto principal:
Fragmentos de Péptidos
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Unión Proteica
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Staphylococcus aureus
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Proteínas Bacterianas
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Fibrinógeno
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Proteínas Portadoras
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Modelos Moleculares
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Química
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Estructura Terciaria de Proteína
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Cristalografía por Rayos X
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Protein & Cell
Año:
2015
Tipo del documento:
Article