Poster Presentation 2014 International Biophysics Congress

Role of calcium binding in T. gondii glideosome (#352)

Marta Enciso 1 , Melanie Williams 2 , Hernan Alonso 2 , Mike Lawrence 2 , Brian Smith 1 , Chris Tonkin 2
  1. La Trobe University, Melbourne, VIC, Australia
  2. Walter and Eliza Hall Institute, Melbourne, VIC, Australia

Toxoplasma gondii is the causative agent of toxoplasmosis and one of the most ubiquitous human pathogens. Like all apicomplexan parasites, host cell invasion and tissue dissemination are seen as the key target to develop new therapeutical strategies. Central to them is gliding motility, the mechanism of apicomplexan motion. It involves a protein complex called glideosome, formed by a single-headed myosin and two light chains attached to it. It has been found that the interaction of one of the two light chains with calcium stabilises and rigidifies the complex, providing the foundation on which the myosin head pivots.

In this communication we combine experiments and simulations to explore the characteristics of this calcium binding and how it affects the gliding motility of the T. gondii glideosome. We have used structural modelling to identify possible calcium-binding residues, as well as those responsible for the interaction among the three proteins of the glideosome complex. Calcium binding affinities have been determined by experiments and simulations.We have also analysed the role of these residues in the overall motion of the parasite by conducting in vivo assays of parasite egress and motility, as well as molecular dynamics simulations. We have identified the key intermolecular interactions that are responsible for the rigidity of the myosin complex, the specific role of each of them in the glideosome and how calcium modulates the parasite motility.