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Publication Abstract from PubMed

Cytochrome c oxidase (CcO), the terminal enzyme in the electron transfer chain, translocates protons across the inner mitochondrial membrane by harnessing the free energy generated by the reduction of oxygen to water. Several redox-coupled proton translocation mechanisms have been proposed, but they lack confirmation, in part from the absence of reliable structural information due to radiation damage artifacts caused by the intense synchrotron radiation. Here we report the room temperature, neutral pH (6.8), damage-free structure of bovine CcO (bCcO) in the carbon monoxide (CO)-bound state at a resolution of 2.3 A, obtained by serial femtosecond X-ray crystallography (SFX) with an X-ray free electron laser. As a comparison, an equivalent structure was obtained at a resolution of 1.95 A, from data collected at a synchrotron light source. In the SFX structure, the CO is coordinated to the heme a3 iron atom, with a bent Fe-C-O angle of approximately 142 degrees . In contrast, in the synchrotron structure, the Fe-CO bond is cleaved; CO relocates to a new site near CuB, which, in turn, moves closer to the heme a3 iron by approximately 0.38 A. Structural comparison reveals that ligand binding to the heme a3 iron in the SFX structure is associated with an allosteric structural transition, involving partial unwinding of the helix-X between heme a and a3, thereby establishing a communication linkage between the two heme groups, setting the stage for proton translocation during the ensuing redox chemistry.

Crystal structure of CO-bound cytochrome c oxidase determined by serial femtosecond X-ray crystallography at room temperature.,Ishigami I, Zatsepin NA, Hikita M, Conrad CE, Nelson G, Coe JD, Basu S, Grant TD, Seaberg MH, Sierra RG, Hunter MS, Fromme P, Fromme R, Yeh SR, Rousseau DL Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):8011-8016. doi:, 10.1073/pnas.1705628114. Epub 2017 Jul 11. PMID:28698372^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.