INVESTIGADORES
SANTOS Javier
congresos y reuniones científicas
Título:
Focusing on Human Frataxin, a Key Mitochondrial Protein Involved in Iron-Sulfur Cluster Biosynthesis
Autor/es:
JAVIER SANTOS
Lugar:
Rio
Reunión:
Congreso; V Latin American Protein Society Meeting 2016; 2016
Institución organizadora:
LPS
Resumen:
Focusing on Human Frataxin, a Key Mitochondrial Protein Involved in Iron-Sulfur Cluster BiosynthesisDr. Javier SantosLaboratory 8, IQUIFIB (CONICET) and the School of Pharmacy and Biochemistry, University of Buenos Aires, Paraguay 2155 C.A.B.A.The possibility of manipulating the biological activity of proteins through delicate modulations of local stabilities and dynamics opens the door for designing new variants and specific drugs. Thus, it sounds feasible to act on the specific stabilization of natural variants intrinsically destabilized observed in a number of diseases, including Friedreich?s Ataxia (FRDA), a rare cardio-neurodegenerative disease caused by alterations of the expression of frataxin (FXN), an essential protein in the mitochondrial metabolism. The aim of our work is to explore the relationship between stability and the structural dynamics of FXN, and we study how these properties are linked to the iron-protein interaction. We explore the effect of point mutations and large sequence changes on the internal mobility of FXN in different timescales, including folding dynamics. Our results show that alterations of loop-1 sequence, which is involved in iron binding, has a significant effect on an extended region of the protein, far from the former, which includes residues from the beta-sheet, some of them associated to the protein-protein interaction process that is important in iron-sulfur cluster biosynthesis. These results point to the existence of communication between different structure elements related to diverse aspects of FXN function. In addition, our group?s previous findings indicate that changes in stability at the C-terminal region give rise to alterations in the structural dynamics of helix alpha 1 and loop-1. These results point to the existence of communication between structure elements crucial for stability and other elements essential for biological activity. We have collectively analyzed the FXN variants, and our findings suggest how a subtle balance between stability and internal mobility may modulate FXN function.