Crystal structures of Bbp from Staphylococcus aureus reveal the ligand binding mechanism with Fibrinogen α.
10.1007/s13238-015-0205-x
- Author:
Xinyue ZHANG
1
;
Meng WU
1
;
Wei ZHUO
1
;
Jinke GU
1
;
Sensen ZHANG
1
;
Jingpeng GE
1
;
Maojun YANG
2
Author Information
1. Key Laboratory for Protein Sciences of Ministry of Education, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
2. Key Laboratory for Protein Sciences of Ministry of Education, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China. maojunyang@tsinghua.edu.cn.
- Publication Type:Journal Article
- Keywords:
Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMM);
Staphylococcus aureus;
bone sialoprotein-binding protein (Bbp);
fibrinogen;
serine-aspartate repeat (Sdr)
- MeSH:
Bacterial Proteins;
chemistry;
genetics;
metabolism;
Carrier Proteins;
chemistry;
genetics;
metabolism;
Crystallography, X-Ray;
Fibrinogen;
metabolism;
Ligands;
Models, Molecular;
Mutation;
Peptide Fragments;
chemistry;
metabolism;
Protein Binding;
Protein Structure, Tertiary;
Staphylococcus aureus
- From:
Protein & Cell
2015;6(10):757-766
- CountryChina
- Language:English
-
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.
