Prof. Dr. Johannes Buchner
Technische Universität München (TUM)
Dept. of Chemistry
Tel: +49 (0) 89 / 289-13341
Fax: +49 (0) 89 / 289-13345
The acquisition of the three dimensional structure of proteins is a highly dynamic process in which the unfolded state, intermediates and the native state are separated by only small differences in energy. We will analyse key processes of the folding and association of a wide-spread topology, the immunoglobulin (Ig) fold. We will focus on two important aspects. The template-assisted folding of an Ig domain will be studied using a novel and unique model system that comprises two highly homologous immunoglobulin domains which form a heterodimer. One of these domains folds completely reversibly, while the other, surprisingly, is natively unfolded. The results will provide important insight into what sets a folding protein apart from a non-folding one with both proteins adopting an almost identical native structure once folded. In the second project, disease-causing amyloidogenic variants of an Ig domain will be analysed with a view to determine how the folding and dynamics are influenced to produce fibrillar structures. The projects rely on the biophysical analysis of folding reactions together with computational approaches and the development of novel single molecule techniques to obtain a comprehensive picture.