期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 29, 页码 12854-12859出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1001839107
关键词
dimer; trimer; protein polymer
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [20051016]
- Japan Society for the Promotion of Science [21350095, 18GS0207]
- Japan Science and Technology Agency
- Sankyo-Foundation of Life Science
- Japanese Aerospace Exploration Agency
- Grants-in-Aid for Scientific Research [20051016, 22657031, 22370061] Funding Source: KAKEN
Cytochrome c (cyt c) is a stable protein that functions in a monomeric state as an electron donor for cytochrome c oxidase. It is also released to the cytosol when permeabilization of the mitochondrial outer membrane occurs at the early stage of apoptosis. For nearly half a century, it has been known that cyt c forms polymers, but the polymerization mechanism remains unknown. We found that cyt c forms polymers by successive domain swapping, where the C-terminal helix is displaced from its original position in the monomer and Met-heme coordination is perturbed significantly. In the crystal structures of dimeric and trimeric cyt c, the C-terminal helices are replaced by the corresponding domain of other cyt c molecules and Met80 is dissociated from the heme. The solution structures of dimeric, trimeric, and tetrameric cyt c were linear based on small-angle X-ray scattering measurements, where the trimeric linear structure shifted toward the cyclic structure by addition of PEG and (NH4)(2)HPO4. The absorption and CD spectra of high-order oligomers (similar to 40 mer) were similar to those of dimericandtrimeric cyt c but different from those of monomeric cyt c. For dimeric, trimeric, and tetrameric cyt c, the Delta H of the oligomer dissociation to monomers was estimated to be about -20 kcal/mol per protomer unit, where Met-heme coordination appears to contribute largely to Delta H. The present results suggest that cyt c polymerization occurs by successive domain swapping, which may be a common mechanism of protein polymerization.
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