6JY3

Monomeric Form of Bovine Heart Cytochrome c Oxidase in the Fully Oxidized State

Summary for 6JY3

• Entry DOI: 10.2210/pdb6jy3/pdb
• Related: 6JY4
• Descriptor: Cytochrome c oxidase subunit 1, Cytochrome c oxidase subunit 7A1, Cytochrome c oxidase subunit 7B, ... (26 entities in total)
• Functional Keywords: monomer, fully oxidized, oxidoreductase
• Biological source: Bos taurus (Bovine); More
• Total number of polymer chains: 13
• Total formula weight: 217032.34

Authors

Shinzawa-Itoh, K.,Muramoto, K. (deposition date: 2019-04-26, release date: 2019-09-18, Last modification date: 2024-11-13)

Primary citation

Shinzawa-Itoh, K.,Sugimura, T.,Misaki, T.,Tadehara, Y.,Yamamoto, S.,Hanada, M.,Yano, N.,Nakagawa, T.,Uene, S.,Yamada, T.,Aoyama, H.,Yamashita, E.,Tsukihara, T.,Yoshikawa, S.,Muramoto, K.
Monomeric structure of an active form of bovine cytochromecoxidase.
Proc.Natl.Acad.Sci.USA, 116:19945-19951, 2019

PubMed Abstract: Cytochrome oxidase (CcO), a membrane enzyme in the respiratory chain, catalyzes oxygen reduction by coupling electron and proton transfer through the enzyme with a proton pump across the membrane. In all crystals reported to date, bovine CcO exists as a dimer with the same intermonomer contacts, whereas CcOs and related enzymes from prokaryotes exist as monomers. Recent structural analyses of the mitochondrial respiratory supercomplex revealed that CcO monomer associates with complex I and complex III, indicating that the monomeric state is functionally important. In this study, we prepared monomeric and dimeric bovine CcO, stabilized using amphipol, and showed that the monomer had high activity. In addition, using a newly synthesized detergent, we determined the oxidized and reduced structures of monomer with resolutions of 1.85 and 1.95 Å, respectively. Structural comparison of the monomer and dimer revealed that a hydrogen bond network of water molecules is formed at the entry surface of the proton transfer pathway, termed the K-pathway, in monomeric CcO, whereas this network is altered in dimeric CcO. Based on these results, we propose that the monomer is the activated form, whereas the dimer can be regarded as a physiological standby form in the mitochondrial membrane. We also determined phospholipid structures based on electron density together with the anomalous scattering effect of phosphorus atoms. Two cardiolipins are found at the interface region of the supercomplex. We discuss formation of the monomeric CcO, dimeric CcO, and supercomplex, as well as their role in regulation of CcO activity.

PubMed: 31533957
DOI: 10.1073/pnas.1907183116

Experimental method

X-RAY DIFFRACTION (1.85 Å)