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O2 migration pathways are not conserved across proteins of a similar fold.

ABSTRACT: Recent advances in computational biology have made it possible to map the complete network and energy profile of gas migration pathways inside proteins. Although networks of O(2) pathways have already been characterized for a small number of proteins, the general properties and locations of these pathways have not been previously compared between proteins. In this study, maps of the O(2) pathways inside 12 monomeric globins were computed. It is found that, despite the conserved tertiary structure fold of the studied globins, the shape and topology of O(2) pathway networks exhibit a large variability between different globins, except when two globins are nearly identical. The locations of the O(2) pathways are, however, found to be correlated with the location of large hydrophobic residues, and a similar correlation is observed in two unrelated protein families: monomeric globins and copper-containing amine oxidases. The results have implications for the evolution of gas pathways in proteins and for protein engineering applications involving modifications of these pathways.

SUBMITTER: Cohen J

PROVIDER: S-EPMC2072066 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

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O2 migration pathways are not conserved across proteins of a similar fold.

Cohen Jordi J Schulten Klaus K

Biophysical journal 20070810 10

Recent advances in computational biology have made it possible to map the complete network and energy profile of gas migration pathways inside proteins. Although networks of O(2) pathways have already been characterized for a small number of proteins, the general properties and locations of these pathways have not been previously compared between proteins. In this study, maps of the O(2) pathways inside 12 monomeric globins were computed. It is found that, despite the conserved tertiary structur ...[more]

PMID: 17693478

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Project description:Most bacteria can generate ATP by respiratory metabolism, in which electrons are shuttled from reduced substrates to terminal electron acceptors, via quinone molecules like ubiquinone. Dioxygen (O2) is the terminal electron acceptor of aerobic respiration and serves as a co-substrate in the biosynthesis of ubiquinone. Here, we characterize a novel, O2-independent pathway for the biosynthesis of ubiquinone. This pathway relies on three proteins, UbiT (YhbT), UbiU (YhbU), and UbiV (YhbV). UbiT contains an SCP2 lipid-binding domain and is likely an accessory factor of the biosynthetic pathway, while UbiU and UbiV (UbiU-UbiV) are involved in hydroxylation reactions and represent a novel class of O2-independent hydroxylases. We demonstrate that UbiU-UbiV form a heterodimer, wherein each protein binds a 4Fe-4S cluster via conserved cysteines that are essential for activity. The UbiT, -U, and -V proteins are found in alpha-, beta-, and gammaproteobacterial clades, including several human pathogens, supporting the widespread distribution of a previously unrecognized capacity to synthesize ubiquinone in the absence of O2 Together, the O2-dependent and O2-independent ubiquinone biosynthesis pathways contribute to optimizing bacterial metabolism over the entire O2 range.IMPORTANCE In order to colonize environments with large O2 gradients or fluctuating O2 levels, bacteria have developed metabolic responses that remain incompletely understood. Such adaptations have been recently linked to antibiotic resistance, virulence, and the capacity to develop in complex ecosystems like the microbiota. Here, we identify a novel pathway for the biosynthesis of ubiquinone, a molecule with a key role in cellular bioenergetics. We link three uncharacterized genes of Escherichia coli to this pathway and show that the pathway functions independently from O2 In contrast, the long-described pathway for ubiquinone biosynthesis requires O2 as a substrate. In fact, we find that many proteobacteria are equipped with the O2-dependent and O2-independent pathways, supporting that they are able to synthesize ubiquinone over the entire O2 range. Overall, we propose that the novel O2-independent pathway is part of the metabolic plasticity developed by proteobacteria to face various environmental O2 levels.

Dataset Information

O2 migration pathways are not conserved across proteins of a similar fold.

Publications

O2 migration pathways are not conserved across proteins of a similar fold.

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