Conformational analysis of the Streptococcus pneumoniae hyaluronate lyase and characterization of Its hyaluronan-specific carbohydrate-binding module
| Autor: | Suits, MDL, Pluvinage, B, Law, A, Liu, Y, Palma, AS, Chai, W, Feizi, T, Boraston, AB |
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| Přispěvatelé: | Wellcome Trust |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
STRUCTURAL BASIS
Biochemistry & Molecular Biology Carbohydrate SURFACE Glycobiology PROTEIN Hyaluronate Lyase Crystallography X-Ray Bacterial Proteins Protein Structure Quaternary Hyaluronan Polysaccharide-Lyases Science & Technology Crystallography integumentary system RECOGNITION Streptococcus SMALL-ANGLE SCATTERING 11 Medical And Health Sciences 06 Biological Sciences Small Angle X-ray Scattering (SAXS) X-RAY-SCATTERING Protein Structure Tertiary BIOLOGICAL MACROMOLECULES Streptococcus pneumoniae GENOME-BASED IDENTIFICATION Carbohydrate Processing Mutagenesis Site-Directed Protein Multimerization VIRULENCE FACTORS Carbohydrate-binding Protein 03 Chemical Sciences Life Sciences & Biomedicine |
| Popis: | For a subset of pathogenic microorganisms, including Streptococcus pneumoniae, the recognition and degradation of host hyaluronan contributes to bacterial spreading through the extracellular matrix and enhancing access to host cell surfaces. The hyaluronate lyase (Hyl) presented on the surface of S. pneumoniae performs this role. Using glycan microarray screening, affinity electrophoresis, and isothermal titration calorimetry we show that the N-terminal module of Hyl is a hyaluronan-specific carbohydrate-binding module (CBM) and the founding member of CBM family 70. The 1.2 Å resolution x-ray crystal structure of CBM70 revealed it to have a β-sandwich fold, similar to other CBMs. The electrostatic properties of the binding site, which was identified by site-directed mutagenesis, are distinct from other CBMs and complementary to its acidic ligand, hyaluronan. Dynamic light scattering and solution small angle x-ray scattering revealed the full-length Hyl protein to exist as a monomer/dimer mixture in solution. Through a detailed analysis of the small angle x-ray scattering data, we report the pseudoatomic solution structures of the monomer and dimer forms of the full-length multimodular Hyl. |
| Databáze: | OpenAIRE |
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