IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
pH effect on the folding mechanism of frataxin from Psychromonas ingrahamii
Autor/es:
ROMAN EA; SANTOS J; CRAIG PO
Lugar:
Villa Carlos Paz, Cordoba
Reunión:
Congreso; Reunion Anual de la Sociedad Argentina de Biofísica; 2013
Institución organizadora:
Sociedad Argentina de Biofísica
Resumen:
Frataxin is a protein that participates in iron binding and delivery to other protein partners. Its absence in humans yields Friedreich´s Ataxia. In our laboratory we study the iron binding and folding mechanism of human and Psychromonas ingrahamii frataxin (pFXN). We previouly reported that pFXN stability is highly modulated by pH in the 6-8 pH range. In this work, we studied the folding reaction of pFXN as a function of pH by computational techniques. We used a coarse grained structure based model suplemented with a general electrostatic potential to extensively sample the folding and unfolding transitions and evaluate pFXN conformational stability. Residues were reduced to 3 atoms over which the bonded and non bonded forces were projected. In this model only the residues that make contact in the native state interact favorably whereas all the others interact only repulsively through excluded volume effect. The model was supplemented with a coulombic electrostatic potential to account for the effect of pH on the stability of the protein. Preliminary results show that protonation of histidine residues highly modulate protein stability. The protonation of key residues and their contribution to the overall effect was also evaluated.