Understanding the dynamics of the membrane-tethered pneumococcal lipoprotein, PsaA

A Schumann-Gillett1,3, E Deplazes1,2, AE Mark1,2 and ML O'Mara3

  1. School of Chemistry and Molecular Biosciences (SCMB), University of Queensland, Queensland, Australia
  2. The Institute for Molecular Biosciences (IMB), University of Queensland, Queensland, Australia
  3. Research School of Chemistry, The Australian National University, Australian Capital Territory, Australia

Pneumonia is the leading cause of infectious death in children worldwide; the World Health Organisation estimates that it killed 922 000 children under 5 in 2015 alone. The primary cause of pneumonia is Streptococcus pneumoniae infection. All serotypes of S. pneumoniae contain a highly conserved membrane-tethered lipoprotein, PsaA, which is the manganese binding protein component of a tripartite manganese ABC import system, PsaBCA. PsaA is an essential virulence factor in S. pneumoniae; its expression is crucial for both cellular adhesion and manganese uptake. A 28-amino acid long region of PsaA, called P4, is believed to mediate adhesion between the bacterium and nasopharyngeal epithelial cells. The interactions between membrane-tethered PsaA and the bacterial cell surface, and the molecular details underpinning P4-mediated adhesion are unknown. We used molecular dynamics simulations to study the interactions between the full-length PsaA lipoprotein and a model bacterial cell membrane. The simulations show that membrane-tethered PsaA consistently adopted the same orientation with respect to the bacterial membrane, which could provide insight into its adhesive and substrate-binding properties.