Poster Presentation The 42nd Lorne Conference on Protein Structure and Function 2017

Structural insight into an evolutionarily ancient programmed cell death regulator – the crystal structure of marine sponge GC-BHP2 bound to LB-Bak-2 (#302)

Sofia Caria 1 , Mark Hinds 1 , Marc Kvansakul 1
  1. La Trobe University, Bundoora, VIC, Australia

Apoptosis or programmed cell death is a crucial response to perturbations in physiological conditions, allowing an organism to determine if a given cell can be eliminated when unneeded, damaged or dangerous for the organism. In this mechanism the B-cell lymphoma 2 (Bcl-2) protein family plays an important role in regulating the homeostasis (Kvansakul et al. 2014).

Sponges are the phylogenetically oldest existent members of the Metazoa phylum. It has been demonstrated that Geodia cydonium (G. cydonium) and Suberites domuncula possesses polypeptide sequences with high sequence similarity to Bcl-2 protein members (Wiens et al. 2000). The study of these proteins is highly relevant for the understanding of the evolution of apoptosis across species. GC-BHP2, a G. cydonium pro-survival Bcl-2 protein, has been shown to be involved in apoptotic pathway (Wiens et al. 2001).

In this study the GC-BHP2 protein biochemical characterisation using ITC as well as its structure determination in complex with a BH3-only peptide from Lubomirskia baicalensis (LB-Bak-2) has enable us to shine light on the sponges apoptosis mechanism and compare it to others previously characterised such as the mammalian and viral. A better understanding of how apoptosis evolved across species might yield value information for rational drug design.

  1. Kvansakul M et al. (2014) Method Enzymol. 544, 44-79
  2. Wiens M et al. (2000) J. Mol. Evol. 50, 520-531
  3. Wiens M et al. (2001) Cell Death Differ. 8, 887-98