TY - JOUR
T1 - Cryo-EM structure of cytochrome bo3 quinol oxidase assembled in peptidiscs reveals an “open” conformation for potential ubiquinone-8 release
AU - Gao, Ye
AU - Zhang, Yue
AU - Hakke, Sneha
AU - Mohren, Ronny
AU - Sijbers, Lyanne J.P.M.
AU - Peters, Peter J.
AU - Ravelli, Raimond B.G.
N1 - Publisher Copyright:
© 2024
PY - 2024/8/1
Y1 - 2024/8/1
N2 - Cytochrome bo3 quinol oxidase belongs to the heme-copper-oxidoreductase (HCO) superfamily, which is part of the respiratory chain and essential for cell survival. While the reaction mechanism of cyt bo3 has been studied extensively over the last decades, specific details about its substrate binding and product release have remained unelucidated due to the lack of structural information. Here, we report a 2.8 Å cryo-electron microscopy structure of cyt bo3 from Escherichia coli assembled in peptidiscs. Our structural model shows a conformation for amino acids 1–41 of subunit I different from all previously published structures while the remaining parts of this enzyme are similar. Our new conformation shows a “U-shape” assembly in contrast to the transmembrane helix, named “TM0”, in other reported structural models. However, TM0 blocks ubiquinone-8 (reaction product) release, suggesting that other cyt bo3 conformations should exist. Our structural model presents experimental evidence for an “open” conformation to facilitate substrate/product exchange. This work helps further understand the reaction cycle of this oxidase, which could be a benefit for potential drug/antibiotic design for health science.
AB - Cytochrome bo3 quinol oxidase belongs to the heme-copper-oxidoreductase (HCO) superfamily, which is part of the respiratory chain and essential for cell survival. While the reaction mechanism of cyt bo3 has been studied extensively over the last decades, specific details about its substrate binding and product release have remained unelucidated due to the lack of structural information. Here, we report a 2.8 Å cryo-electron microscopy structure of cyt bo3 from Escherichia coli assembled in peptidiscs. Our structural model shows a conformation for amino acids 1–41 of subunit I different from all previously published structures while the remaining parts of this enzyme are similar. Our new conformation shows a “U-shape” assembly in contrast to the transmembrane helix, named “TM0”, in other reported structural models. However, TM0 blocks ubiquinone-8 (reaction product) release, suggesting that other cyt bo3 conformations should exist. Our structural model presents experimental evidence for an “open” conformation to facilitate substrate/product exchange. This work helps further understand the reaction cycle of this oxidase, which could be a benefit for potential drug/antibiotic design for health science.
KW - Cytochrome oxidase
KW - Escherichia coli (E. coli)
KW - Ni-NTA resin
KW - Peptidisc
KW - Single particle analysis
KW - Ubiquinone
U2 - 10.1016/j.bbabio.2024.149045
DO - 10.1016/j.bbabio.2024.149045
M3 - Article
SN - 0005-2728
VL - 1865
JO - Biochimica et Biophysica Acta-bioenergetics
JF - Biochimica et Biophysica Acta-bioenergetics
IS - 3
M1 - 149045
ER -