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Featured Event

9/18 - Seminar (chem bio): Ekaterina Pletneva, Dartmouth

Ekaterina Pletneva - speaker's website
Department of Chemistry
Host: Jay Groves

Becoming a peroxidase: conformational dynamics of a membrane-bound
cytochrome c

Interactions of cytochrome c (cyt c) with a mitochondrial membrane cardiolipin (CL) are important for both electron transfer and apoptotic functions of this protein. A sluggish peroxidase in its native state, when bound to CL, cyt c catalyzes CL peroxidation, which contributes to the protein apoptotic release. The details of the cyt c-CL interactions, however, are not clear, even more in living systems. The heterogeneous CL-bound cyt c ensemble is difficult to characterize with traditional structural methods and ensemble-averaged probes. We have employed time-resolved FRET measurements and fluorescence correlation spectroscopy (FCS) to evaluate structural properties of the CL-bound protein in dye-labeled variants of cyt c. Dye-to-heme distance distributions reveal a conformational diversity of the CL-bound cyt c ensemble with distinct populations of the polypeptide structures that vary in their degree of protein unfolding. A fraction of the ensemble is substantially unfolded; these largely open cyt c structures likely dominate the peroxidase activity of the CL-bound cyt c ensemble. We analyze the sequence of the protein unfolding events and effects of physiological modulators on the cyt c ensemble. Experiments with biological membranes test the developed mechanistic model in vivo.