Structural characterization of human apolipoprotein A-I (apoA-I) variants associated with amyloidosis
Nahuel Alberto Ramella
Laboratory of Cellular Dynamics, Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry.
Non-variant apolipoprotein A-I is found deposited in senile atherosclerotic arteries, but in addition certain natural single mutations, as Lys107-0 and Gly26Arg, favor its pathologic aggregation causing serious organ damage depending on its localization. During my thesis Project, I extensively studied the influence of different micro environmental factors on the folding and aggregation of the apoA-I variants mentioned above. Interestingly, in many technical approaches Gly26Arg behaves similarly to the Wild type (Wt) form, suggesting the need to look for more sensitive experimental designs to explore protein structure. In this proposal I attempt to characterize key structural features that determine the amyloidogenic propensity of apoA-I. The microenvironment-sensitive properties of a new family of fluorescent probes recently developed at Dr Jovin’s lab, offer the unique possibility for establishing the existence and transitions between distinct conformational states and aggregation intermediates. In addition, the novel fluorescence and atomic force microscopy available in his lab will help to characterize protein aggregates conformation. I believe my visit to Dr Jovin’s lab will be extremely important not only to finish my thesis Project, but especially to interact with one of the most Outstanding Researchers in this field.