- Featuring expert speakers from Instruct Centres across Europe, the Instruct-ERIC webinar series highlights some of the latest developments in structural biology, demonstrating how integrative methods enable scientists to decipher the mechanisms that underpin health and disease. Dr. Gabriel Zoldak introduced the Center for interdisciplnary biosciences to the broad community of INSTRUCT Centers as well as described the latest achievements in the development of single-molecule protein biophysics at the CIB. In his presentation, he talked about about his recently published paper on a pathological variant of -light chain. The study examined the relationship between stability and time-dependent solubility of the recombinant human antibody light chain, hLC, which was found to form renal tubular casts in the multiple myeloma patient. By the combination of experimental assays at different temperatures, different protein concentrations and kinetic modeling using ordinary differential equations, we were able to extrapolate time-dependent protein solubility to temperatures where both unfolding and aggregation processes are strongly kinetically coupled. The study enables mechanism-based evaluation and interpretation of different physico-chemical factors contributing to the hLC unfolding and aggregation and their effect on the formation of extracellular protein deposits. In the future, the scientists plan to extend their investigations by newly established single-molecule techniques.
