The interplay between structure and function of proteins: towards the development of translational tools for disease related proteins.

HERRERA MARIA GEORGINA; PIGNATARO, MARÍA FLORENCIA; SANTOS JAVIER

Caparica

Conferencia; 4th International Caparica Christmas Conference on Translational Chemistry; 2021

The determination of protein structure and their physicochemical properties has a predominant role in connecting the chemical and biological worlds [1]. In particular, this is reflected in the case of proteins related-diseases, in which the lack of this molecule or changes in its stability/conformation may induce pathology [2]. Also, the conformational information obtained from proteins has highly contributed to the development, at different levels, of chemical and biological tools. With this perspective, we will describe our results on the conformational study of human frataxin, a protein involved in the Fe-S clusters biogenesis which its malfunction produces the neurodegenerative disorder called Friedreich Ataxia [3], and TDP-43, which aggregation generates Amyotrophic Lateral Sclerosis. We will present our results on the structural analysis of both proteins, their particular supramolecular behaviour and their interactions with other proteins and biomolecules. This information is of key relevance in understanding the molecular mechanisms of diseases and the development of chemical and biological strategies for therapeutics. In this sense, we will also present a successful approach implemented in our group to engineering different frataxin binding proteins. We will describe the selection and production of these protein binders based on the Sac7d protein scaffold [4]. These molecules could be implemented as a biochemical tool to explore protein binding, stability and function in the near future, connecting chemistry and biology with a translational perspective towards human health.