The Statistical Conformation of a Highly Flexible Protein: Small-Angle X-Ray Scattering of S. aureus Protein A

• SAXS data for Staphylococcal protein A (SpA) are fit to a new polymer physics model
• The best-fit model is minimally parameterized to match SAXS information content
• SpA is a flexible protein that sweeps a 90 Å hemisphere on the cell surface
• Protocol is proposed for matching model complexity to SAXS data information content

SummaryStaphylococcal protein A (SpA) is a multidomain protein consisting of five globular IgG binding domains separated by a conserved six- to nine-residue flexible linker. We collected SAXS data on the N-terminal protein-binding half of SpA (SpA-N) and constructs consisting of one to five domain modules in order to determine statistical conformation of this important S. aureus virulence factor. We fit the SAXS data to a scattering function based on a new polymer physics model, which provides an analytical description of the SpA-N statistical conformation. We describe a protocol for systematically determining the appropriate level of modeling to fit a SAXS data set based on goodness of fit and whether the addition of parameters improves it. In the case of SpA-N, the analytical polymer physics description provides a depiction of the statistical conformation of a flexible protein that, while lacking atomistic detail, properly reflects the information content of the data.

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