Crystal structure of Streptococcus pneumoniae pneumolysin provides key insights into early steps of pore formation
| Autor: | Sara L. Lawrence, Michael W. Parker, Rodney K. Tweten, Terrence D. Mulhern, Susanne C. Feil, Craig J. Morton, Kristin R. Wade, Allison J. Farrand, Michael A. Gorman |
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| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Protein Conformation Carbohydrates Plasma protein binding Biology Cholesterol-dependent cytolysin medicine.disease_cause Crystallography X-Ray Virulence factor Article Microbiology 03 medical and health sciences Structure-Activity Relationship 0302 clinical medicine Protein structure Bacterial Proteins Streptococcus pneumoniae medicine 030304 developmental biology 0303 health sciences Multidisciplinary Pneumolysin Binding Sites Small molecule 3. Good health Molecular Docking Simulation Solutions Membrane Mutation Streptolysins Protein Multimerization Mannose 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Pore-forming proteins are weapons often used by bacterial pathogens to breach the membrane barrier of target cells. Despite their critical role in infection important structural aspects of the mechanism of how these proteins assemble into pores remain unknown. Streptococcus pneumoniae is the world’s leading cause of pneumonia, meningitis, bacteremia and otitis media. Pneumolysin (PLY) is a major virulence factor of S. pneumoniae and a target for both small molecule drug development and vaccines. PLY is a member of the cholesterol-dependent cytolysins (CDCs), a family of pore-forming toxins that form gigantic pores in cell membranes. Here we present the structure of PLY determined by X-ray crystallography and, in solution, by small-angle X-ray scattering. The crystal structure reveals PLY assembles as a linear oligomer that provides key structural insights into the poorly understood early monomer-monomer interactions of CDCs at the membrane surface. |
| Databáze: | OpenAIRE |
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