Multiscale Conformational Heterogeneity in Staphylococcal Protein A: Possible Determinant of Functional Plasticity
Autor: | David S. Richardson, Yang Qi, Charles W. Pemble, Jane S. Richardson, Terrence G. Oas, Lindsay N. Deis, Andrew Hagarman |
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Rok vydání: | 2014 |
Předmět: |
Models
Molecular Staphylococcus aureus Protein Conformation Staphylococcal protein Computational biology Plasma protein binding Biology Crystallography X-Ray Article Virulence factor Protein tertiary structure Protein Structure Tertiary Protein structure Biochemistry Structural Biology Side chain Staphylococcal Protein A Molecular Biology Linker Binding domain |
Zdroj: | Structure. 22:1467-1477 |
ISSN: | 0969-2126 |
DOI: | 10.1016/j.str.2014.08.014 |
Popis: | The Staphylococcus aureus virulence factor staphylococcal protein A (SpA) is a major contributor to bacterial evasion of the host immune system, through high-affinity binding to host proteins such as antibodies. SpA includes five small three-helix-bundle domains (E-D-A-B-C) separated by conserved flexible linkers. Prior attempts to crystallize individual domains in the absence of a binding partner have apparently been unsuccessful. There have also been no previous structures of tandem domains. Here we report the high-resolution crystal structures of a single C domain, and of two B domains connected by the conserved linker. Both structures exhibit extensive multiscale conformational heterogeneity, which required novel modeling protocols. Comparison of domain structures shows that helix1 orientation is especially heterogeneous, coordinated with changes in side chain conformational networks and contacting protein interfaces. This represents the kind of structural plasticity that could enable SpA to bind multiple partners. |
Databáze: | OpenAIRE |
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