EARLY STAGES OF THERMAL AGGREG OF CONCANAVALIN A: AMYLOID & AMORPH FORMATIONS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. FULL TITLE: Early stages of thermal aggregation of Concanavalin A: amyloid and amorphous aggregates formation. Concanavalin A is a protein belonging to the legume lectins family. Its quaternary structure is governed by a dimer tetramer equilibrium, strongly affected by pH and temperature, and the secondary structure is mainly composed of beta sheets, with no alpha helical regions. The protein is known to be able to induce programmed cell death in cortical neurons, by a mechanism which displays remarkable analogies with the amyloid beta peptide induced programmed cell death.We found that the aggregation process may evolve through two distinct pathways leading, respectively, to the formation of amyloid or amorphous aggregates. The relative extent of the two pathways is determined by pH, as amyloid aggregation is favored at high pH values, while the formation of amorphous aggregates is favored at low pH. These results can help to understand the influence of external conditions on different aggregation pathways. We want to further analyze the aggregation pathway of this protein focusing in physiological conditions in order to ascertain if and how amyloid formation is involved in cell death.