Serotype 3 pneumococci sequester platelet-derived human thrombospondin-1 via the adhesin and immune evasion protein Hic
| Autor: | Sylvia Kohler, Krystin Krauel, Ulrike Binsker, Johanna Habermeyer, Hansjörg Schwertz, Thomas P. Kohler, Sven Hammerschmidt |
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| Rok vydání: | 2017 |
| Předmět: |
Blood Platelets
0301 basic medicine endocrine system Plasma protein binding Biology medicine.disease_cause Biochemistry Microbiology Thrombospondin 1 Extracellular matrix 03 medical and health sciences Immune system Bacterial Proteins Streptococcus pneumoniae medicine Humans Adhesins Bacterial Molecular Biology Thrombospondin 030102 biochemistry & molecular biology Molecular Bases of Disease Cell Biology Cell biology Bacterial adhesin 030104 developmental biology biology.protein Vitronectin Carrier Proteins Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 292:5770-5783 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m116.760504 |
| Popis: | Streptococcus pneumoniae serotype 3 strains emerge frequently within clinical isolates of invasive diseases. Bacterial invasion into deeper tissues is associated with colonization and immune evasion mechanisms. Thus, pneumococci express a versatile repertoire of surface proteins sequestering and interacting specifically with components of the human extracellular matrix and serum. Hic, a PspC-like pneumococcal surface protein, possesses vitronectin and factor H binding activity. Here, we show that heterologously expressed Hic domains interact, similar to the classical PspC molecule, with human matricellular thrombospondin-1 (hTSP-1). Binding studies with isolated human thrombospondin-1 and various Hic domains suggest that the interaction between hTSP-1 and Hic differs from binding to vitronectin and factor H. Binding of Hic to hTSP-1 is inhibited by heparin and chondroitin sulfate A, indicating binding to the N-terminal globular domain or type I repeats of hTSP-1. Competitive inhibition experiments with other pneumococcal hTSP-1 adhesins demonstrated that PspC and PspC-like Hic recognize similar domains, whereas PavB and Hic can bind simultaneously to hTSP-1. In conclusion, Hic binds specifically hTSP-1; however, truncation in the N-terminal part of Hic decreases the binding activity, suggesting that the full length of the α-helical regions of Hic is required for an optimal interaction. |
| Databáze: | OpenAIRE |
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