Final Report Summary - DYNALLO (Towards a Dynamical Understanding of Allostery)
Allostery is the switching of the function of a protein upon binding of a ligand at a particular binding site. As such, allosteric proteins can be viewed as the “transistors” of life, and complex feedback networks of many such molecular switches ultimately make a living cell. The goal was to understand the dynamics of the switching on an atomistic level. As the switching is fast (i.e. 100 ns, as we now know), its observation requires a trigger that is even faster. To that end, we linked a small organic molecule used as a photo-switch (an azobenzene derivative) across the binding groove of a well-studied prototype allosteric protein (the PDZ2 domain). The photo-switch can be switched between two conformations by short laser pulses on a very fast, picosecond timescale. It is linked to the protein in such a way that the conformational change of the photo-switch induces a conformational change in the protein that mimics that of ligand binding in the natural system. That molecular construct allows us to study the switching process in unprecedented detail by transient IR spectroscopy, e.g. the response time of the protein as well as the propagation of a signal through the protein.