Poster Presentation The 48th Lorne Conference on Protein Structure and Function 2023

Structures of Periscope Protein lectin-like adhesins Aap, SasG and Pls infer a non-canonical interaction with the host cell (#428)

Laura C. Clark 1 , Kate E. Atkin 1 , Fiona Whelan 2 , Gemma Harris 1 , Samuel C. Griffiths 1 , Jennifer R. Potts 3
  1. Department of Biology, University of York, York, North Yorkshire, United Kingdom
  2. Department of Molecular and Biomedical Science, School of Biological Sciences, University of Adelaide, SA, Australia
  3. School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia

Staphylococcus aureus and Staphylococcus epidermidis are frequently associated with medical device infections that involving biofilm formation on the device surface. Biofilm formation and host colonisation have been linked to staphylococcal surface proteins Aap, SasG and Pls. These surface proteins are members of the Periscope Protein class, comprising a repetitive region (“B region”) and an N-terminal host colonisation region ("A region") [1]. The host colonisation region has been predicted to incorporate a lectin-homology fold, typically associated with glycan binding. We previously showed that repetitive regions comprised of E-G5-domains (as found in Aap, SasG and Pls) can form highly elongated structures [2]. In the context of a Periscope Protein, length variation of the central repetitive region has been predicted to result in projection of the host colonisation domain at variable distances from the bacterial cell surface. We have determined the structures of the host colonisation lectin domains of SasG, Aap and Pls and a lower resolution structure of the Aap lectin domain with contiguous E-G5 repeats. The proximity of the N- and C-termini of the lectin domains suggests that the adhesin fold will be positioned at the cell distal tip of the variable length rod. Previously, proteolytic cleavage or a deletion within the A-region have been shown to induce biofilm formation. The structures we have determined here infer a potential link between these observations. Interestingly, like the canonical lectin fold, the Aap, SasG and Pls A domains bind a metal ion, but feature one key difference that indicates a non-canonical ligand binding mechanism may underpin bacterial adhesion to the host.

  1. Macintosh, R. L., Brittan, J. L., Bhattacharya, R., Jenkinson, H. F., Derrick, J., Upton, M., and Handley, P. S. (2009) The terminal A domain of the fibrillar accumulation-associated protein (Aap) of Staphylococcus epidermidis mediates adhesion to human corneocytes. J Bacteriol 191, 7007-7016
  2. Whelan, F., Lafita, A., Gilburt, J., Degut, C., Griffiths, S. C., Jenkins, H. T., St John, A. N., Paci, E., Moir, J. W. B., Plevin, M. J., Baumann, C. G., Bateman, A., and Potts, J. R. (2021) Periscope Proteins are variable-length regulators of bacterial cell surface interactions. Proc Natl Acad Sci U S A 118, e2101349118