Mawadda Alghrably

King Abdullah University of Science and Technology, Saudi Arabia

Title: Interaction of amylin species with Copper

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Biography

Mawadda Alghrably is a PhD candidate at King Abdullah University of Science and Technology (KAUST), Jeddah, Saudi Arabia. She obtained her Master’s degree in Cellular and Molecular Biology from the same university in 2019. She works currently with professor Mariusz Jaremko, her work is focusing on understanding and describing the biological phenomena which rule the protein folding and dynamics, as well as the behavior of peptides under different conditions, using NMR spectroscopy and other biophysical tools

Abstract

Protein aggregation has attracted substantial interest because of its role in causing several illnesses, such as neurodegenerative diseases and type II diabetes. Recently, it has been shown that protein aggregation can be prevented by forming metal ion complexes with a target protein, which affects their conformation and physical properties. Thus, understanding the interactions between aggregating molecules and metal ions is beneficial for new drug discovery.

Human Islet Amyloid Polypeptide (hIAPP) or human amylin, is known for its complementary role to insulin, in maintaining blood glucose levels in the human body. hIAPP has a high tendency to aggregate, this characteristic is primarily associated with type II diabetes. On the other hand, hIAPP analogues, Pramlintide, and Rat amylin are known to be resistant to aggregation due to the presence of proline residues, which are usually ?-sheet “breakers” within their amino acid sequence.

Here, we will introduce hIAPP and its analogues. Then, we will show my work on the investigation of Cu²⁺ coordination properties of pramlintide and rat amylin using nuclear magnetic resonance. Furthermore, We will provide some results of thioflavin T assays and TEM, that shows the influence of Cu²⁺ on the aggregation properties of these analogues.

We find that both peptides form stable complexes with Cu²⁺ with similar affinities. The N-termini of both peptides are involved in Cu²⁺ binding; His18 imidazole is an equally attractive binding site in the case of pramlintide. Our results show that Cu²⁺ ions influence the aggregation of pramlintide, but not that of rat amylin.