 |
Storage form (24-mer) and active forms of αB-crystallin which protect against cataract
|
In 2009, in very close collaboration with Sevil Weinkauf, professor for electron microscopy at the Technische Universitaet Muenchen, the first part of the αB-crystallin puzzle fell into place. The team successfully deciphered the molecular structure of the most important form of this versatile protein – a molecule comprising 24 subunits. Under normal conditions, i.e. when the cell is not exposed to stress, this complex is the most common variant. However, it is merely an idle form that contributes little to the prevention of clumping in other proteins. It was clear that there must be another molecular switch that triggers the protective protein.
It is this trigger mechanism that the team headed by Buchner and Weinkauf uncovered now. When a cell is exposed to stress, for instance when subjected to heat, phosphate groups are attached to a specific region of the protein. The negative charges of these phosphates break the links between the subunits and the large complexes consequently disintegrate into numerous smaller ones of only six or twelve subunits each. As a result of this breakup, the regions at the ends of the complexes become more flexible allowing the molecules to dock up with different partners, thereby preventing them from clumping – the protective protein is now active.
