Protein-SAM Interactions Delay the Alkaline Transition of Cytochrome c

OVIEDO ROUCO, SANTIAGO; SZUSTER, JONATHAN; ÁLVAREZ PAGGI, DAMIÁN; TOMASINA, FLORENCIA; DEMICHELI, VERÓNICA; TÓRTORA, VERÓNICA; BATTHYANY, CARLOS; RADI, RAFAEL; MURGIDA, DANIEL H.

Chascomús

Congreso; IV Latin American Meeting on Biological Inorganic Chemistry - V WOQUIBIO; 2014

Cytochomec (Cyt) is a soluble mitochondrial protein that switches between shuttling electrons at the mitochondrial respiratory chainand participating in programmed cell death (apoptosis). Both the mechanisms that trigger the alternative function switching and the steps that lead to apoptosis have become subjects of intensive research. It has been postulated that nitration of tyrosine 74 (Tyr74) elicits an early alkaline transition of Cyt, in which the axial methionine ligand (Met80) is replaced by one of the superficial lysine residues (Lys72 or Lys79). This alkaline form has been proposed as a key player in the onset of apoptosis, by means of its putative peroxidase activity. Cyt may associate with thecardiolipindomains of the mitochondrial membrane, peroxidase the constituent phospholipid and translocate to the cytoplasm, triggering apoptosis. Most parameters of the alkaline transition have been measured in solution. Our goal is to characterize the thermodynamics and kinetics of the alkaline transition of Cyt in a biomimetic environment that captures the essence of the membrane-protein interactions.