It is this similarity that gives to arsenate its high biological toxicity. However, some microscopic organisms survive in arsenate rich environments. In 2011, a team of the NASA hypothesised in the American journal Science that one of these organisms, Halomonas GFAJ-1 (Mono Lake, California, USA), uses and incorporates arsenate in its DNA, thus replacing the phosphate and constituting an alternative form of life (Wolfe-Simon et al., 2011). Since then, this hypothesis was refuted by two studies, recently published in Science (Erb et al., 2012; Reaves et al., 2012); however the exceptional resistance of this organism to the arsenate is highlighted. The mechanism of survival in the presence of high concentrations of arsenate, such as in the Mono Lake, remains unknown. Indeed, to date, there is no identified protein able to distinguish effectively phosphate from arsenate.
In 2009, Mikael Elias, PhD under the supervision of Prof. Eric Chabrière, team leader in the prestigious Rickettsiae Unit of Prof. Didier Raoult at the Faculty of Medicine of Marseilles, has published the phosphate’s mechanism of fixation within bacterial carrying, in the journal of chemistry Journal of the American Chemical Society. Dr. Elias continued his work at the Weizmann Institute of Science (Israel) with Prof. Dan Tawfik, Prof. Eric Chabrière and in collaboration with the ETH Zurich (Switzerland).
The study published in the prestigious journal Nature focuses on proteins called pstS, which import phosphate from the environment into the cell. These studies demonstrate that they have the unique ability to distinguish phosphate and arsenate. Thanks to the structural data at ultra-high resolution that were obtained, the molecular mechanism responsible for this differentiation was elucidated. Surprisingly, the differentiation is mainly based on a unique hyper specific interaction that can be optimum only with phosphate and not with arsenate, and this because of their tiny difference of size (4% in volume). This first-time specificity explains the resistance of some organisms to arsenate and their survival in these extreme environments. Moreover the study shows that this specificity can be further increased. Indeed, the analysis of pstS of the Halomonas GFAJ-1 bacterium, organism extremely resistant to arsenate, is about 10 times more efficient than all other proteins tested to distinguish arsenate. This increased capacity suggests that these proteins have evolved specifically to be extremely selective.
Furthermore, highlighting this unique example of specificity could also provide a better understanding of the interactions between protein and ligand and the keys to their specificity. This knowledge could then be used to develop or improve some therapeutic molecules.
Elias M, Wellner A, Goldin-Azulay K, Chabriere E, Vorholt JA, Erb TJ, Tawfik DS. The molecular basis of phosphate discrimination in arsenate-rich environments. Nature, 2012 Oct 3. (epub ahead of print)