Probing the interplay between calcitonins and islet amyloid polypeptides with membranes using advanced fluorescence methodologies

Joana Catarina Ribeiro Ricardo

Key information

Authors:

Joana Catarina Ribeiro Ricardo (Joana Catarina Ribeiro Ricardo)

Supervisors:

Ana Isabel Abrantes Coutinho (Ana Isabel Abrantes Coutinho); Manuel José Estevez Prieto (Manuel José Estevez Prieto)

Published in

03/22/2019

Abstract

The conversion of peptides/proteins from their native soluble states into β-sheet-rich fibrillar assemblies is the hallmark of several human diseases. Biological membranes can modulate amyloid fibril formation in vivo, increasing its complexity. Here, calcitonin (CT) and islet amyloid polypeptide (IAPP) were used as model polypeptides to obtain a mechanistic understanding of how anionic lipid membranes influence their fibrillation pathways. Comparative biophysical studies of the selfassembly of the human amyloidogenic (hCT and hIAPP, respectively) and a control non-amyloidogenic variant of each peptide (salmon (sCT) and rat (rIAPP) sequences, respectively) were performed to elucidate the structural and dynamic features of the oligomeric intermediates formed in each case. Fluorescent conjugates of the peptides were used to increase the scope of the applied advanced fluorescence techniques.