The Proline/Glycine-Rich Region of the Biofilm Adhesion Protein Aap Forms an Extended Stalk that Resists Compaction
Date
2017-01
Authors
Yarawsky, Alexander
English, Lance R.
Whitten, Steven T.
Herr, Andrew
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
Staphylococcus epidermidis is one of the primary bacterial species responsible for healthcare-associated infections. The most significant virulence factor for S. epidermidis is its ability to form a biofilm, which renders the bacteria highly resistant to host immune responses and antibiotic action. Intercellular adhesion within the biofilm is mediated by the accumulation-associated protein (Aap), a cell wall-anchored protein that self-assembles in a zinc-dependent manner. The C-terminal portion of Aap contains a 135-aa-long, proline/glycine-rich region (PGR) that has not yet been characterized. The region contains a set of 18 nearly identical AEPGKP repeats. Analysis of the PGR using biophysical techniques demonstrated the region is a highly extended, intrinsically disordered polypeptide with unusually high polyproline type II helix propensity. In contrast to many intrinsically disordered polypeptides, there was a minimal temperature dependence of the global conformational state of PGR in solution as measured by analytical ultracentrifugation and dynamic light scattering. Furthermore, PGR was resistant to conformational collapse or α-helix formation upon the addition of the osmolyte trimethylamine N-oxide or the cosolvent 2,2,2-trifluoroethanol. Collectively, these results suggest PGR functions as a resilient, extended stalk that projects the rest of Aap outward from the bacterial cell wall, promoting intercellular adhesion between cells in the biofilm. This work sheds light on regions of low complexity often found near the attachment point of bacterial cell wall-anchored proteins.
Description
Keywords
analytical ultracentrifugation, cell wall-anchored protein, circular dichroism, intrinsically disordered protein, staphylococcus epidermidis
Citation
Yarawsky, A. E., English, L. R., Whitten, S. T., & Herr, A. B. (2017). The proline/glycine-rich region of the biofilm adhesion protein Aap forms an extended stalk that resists compaction. Journal of Molecular Biology, 429(2), pp. 261–279.