Astrobiology Science and Technology for Exploring Planets (ASTEP)

Understanding how the molecules of life adapt to extreme environments is the central theme to this project. Our premise is that protein stability can be partially understood by examining the amino acid make up of α-helices. One of the main factors that controls α-helix stability is the presence of intra-helical noncovalent bonding interactions such as salt bridges. These interactions exist in thermodynamic equilibria, and as such, the strength of the interaction will be strongly influenced by the physical factors of the environment. Therefore, organisms from different environments would be expected to use different types of intra-helical interactions to adapt to their specific environment. To explore this question, we have developed a bioinformatics tool that couples α-helix prediction to a motif search engine that generates an envirogenic fingerprint of the distributions of intra-helical interactions in the proteins of a given DNA sample. This program has been used for a comparative analysis of a number of extremophilic and mesophilic organisms and has been able to successfully group organisms as a function of their environment of origin, confirming that helix-stabilizing interactions are signature to a given environment. To take this project to the next level, we are currently working on understanding how specific motifs act to stabilize or destabilize a protein toward extreme environments. To do this, we have established a collaboration with Dr. George Bachand of the Center for Integrated Nanotechnology at Sandia National Labs. Dr. Bachand has a background in protein engineering, and in conjunction with him and members of his group, we have designed a series of mutants of the motor protein kinesin (Figure 1) that add new potentially α-helix stabilizing motifs to the wilt type protein. This project is ongoing, and we are nearing the point to where we will be studying a variety of kinesin mutants.

Figure 1. Crystal structure of the motor protein Kinesin.