Heme Ruffling in Cytochrome c As a Mechanism to Control Electron Transfer

Thursday, 28 May 2015: 09:40
Lake Michigan (Hilton Chicago)
P. M. Champion (Northeastern University)
Recent studies of a variety of heme protein systems demonstrate that impulsively driven Raman vibrational coherence (or vibrational coherence spectroscopy) is a sensitive probe of thermally accessible and functionally relevant distortions of the active site heme chromophore. The observed signals involve otherwise symmetry forbidden optically driven coherent motions that become allowed due to protein-induced distortions of the heme along its out-of-plane normal modes. The low frequency (ℏω < kBT~300K~200 cm-1) of such modes allow the efficient extraction of energy from the thermal bath so that it can be utilized it for barrier crossing. An example of such a situation is the heme doming motion, which is a key reaction coordinate for ligand binding. Generally, the low frequency out-of-plane modes of the heme are prime candidates to serve as biochemical reaction coordinates. The mixing with other delocalized low-frequency modes of the protein, or with binding partners, offers a potential control mechanism.

In order to probe the effect of heme “ruffling” on electron transport, we studied three cytochromes that display a wide variation in the protein-induced distortion along this mode1. As the ruffling distortion is increased, the ruffling mode frequency decreases from ~ 60 cm-1 to ~ 45 cm-1.  The photoreduction cross-section is also measured and found to decrease exponentially as a function of the magnitude of the distortion. Given the similarity in the distance between the heme and the nearest aromatic amino acid for all three proteins, the order-of-magnitude changes in photoreduction rate demonstrate that the ruffling coordinate can serve as a control mechanism for electron transport in heme proteins. For example, major differences in heme ruffling are noted for cytochrome c when bound to the mitochondrial membrane compared to its solution structure.

1.  Y. Sun, A. Benabbas, W. Zeng, J. Kleingardner, K. Bren, and P. M. Champion, Proc. Natl. Acad. Sci.(USA) 111, 6570-6575 (2014).