Protein aggregation has been investigated in much mechanistic, structural and thermodynamic detail, by both experimentalists and theoreticians,owing to its complexityand association with several neurodegenerative diseases like Alzheimers’, Parkinson’s, prion diseasesetc. The process of protein aggregation broadly features: (a) association of monomers to form high molecular weight multimersand (b) misfolding into β-sheet rich structures with no resemblance to the starting form whatsoever in many cases.Prion proteins, due to their association with a group of infectious diseases together known as “spongiform encephalopathies”has been the subject of intense researchfor several years. Under pathological conditions, the alpha-helical prion monomerconverts irreversibly into a β-sheet rich multimeric species. In the laboratory, this conformational conversion process can be mimickedsuccessfully, makingit an excellent model system for protein aggregation experiments.However, lab-grown prion aggregates are not as infectious as their cellular pathogenic counterparts.In my talk, I will describethe in-vitro misfolding of the mouse prion proteinaccompanying its oligomerization at low pH. From intramolecular ensemble FRET-monitored kinetic data,supplemented with oligomerization kinetics and kinetic modelling analysis, conformational changes across different secondary and tertiary structural segments of the mouse prion protein (moPrP), after the monomeric units transformed into large oligomers OL, which subsequently disaggregated reversibly into small oligomers OSat pH 4, were investigated. The sequence segments spanning helices α2 and α3 underwent a compaction during the formation of OLand elongation into β-sheets during the formation of OS. The β1-α1-β2 and α2-α3 subdomainswere separated, and the helix α1 was unfolded to varying extents in both OLand OS