The human frataxin variants found in carcinoma cells display different functional activity and conformational stability compared to the wild type enzyme.

Proponente Roberta Chiaraluce - Professore Associato
Sottosettore ERC del proponente del progetto
Componenti gruppo di ricerca

The most common cause of protein loss of function is the destabilization of its native structure, hence the decrease of its thermodynamic stability. Experimental studies on thermodynamic stability of some natural missense protein variants expressed in cancer tissues reveal a decrease in thermal stability and an increase of protein flexibility. The expression of these single residue variants (SRVs) is caused by non synonymous single nucleotide polymorphisms (nsSNPs) that occurr in the DNA coding region and encode a change in the amino acid sequence. The single amino acid substitution can potentially affect the protein structure-function relationships in different ways, such as changes in protein function, stability, flexibility and interaction with other proteins, nucleic acids, and other molecules. Several investigations have addressed the effect of SRV on protein stability, functions and interactions. The stability of the SRVs has been considered to be responsible of the impact of the mutation on the pathological conditions or on the genetic susceptibility to diseases. The aim of this project is the study of some natural SRVs of human frataxin (hFXN), an iron binding protein involved in iron-sulfur cluster assembly. In this study we will select some natural SRV, of hFXN that are expressed in cancer tissues and reported in COSMIC database. These variants will be characterized to investigate the effect of single amino acid substitution on hFXN thermal and thermodynamic stability and structure in solution.

LS1_2, LS1_1

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