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Structural mechanism coupling the reduction of oxygen to proton pumping in living cells

Objective

Every breath you take delivers oxygen to mitochondria within the cells of your body. Mitochondria are energy transducing organelles that accept electrons liberated from the food that you eat in order to generate a transmembrane proton concentration gradient. Cytochrome c oxidase is an integral membrane protein complex in the mitochondria that accepts four electrons and reduces molecular oxygen to two water molecules while simultaneously pumping protons against a transmembrane potential. Cytochrome c oxidase homologues are found in almost all living organisms. Because oxygen is the final destination of the transferred electrons, this enzyme family is referred to as the terminal oxidases. Crystal structures of terminal oxidases have been known for more than two decades and these enzymes have been studied with virtually all biophysical and biochemical methods. Despite this scrutiny, it is unknown how redox reactions at the enzyme’s active site are coupled to proton pumping. Here I aim to create a three dimensional movie that reveals how proton exchange between key amino acid residues is controlled by the movements of electrons within the enzyme. This work will utilize state-of-the-art methods of time-resolved serial crystallography, time-resolved wide angle X-ray scattering and time-resolved X-ray emission spectroscopy at European X-ray free electron lasers (XFELs) and synchrotron radiation facilities to observe structural changes in terminal oxidases with time. I will develop new approaches for rapidly delivering oxygen or electrons into the protein’s active site in order to initiate the catalytic cycle in microcrystals and in solution. This project will yield completely new insight into one of the most important chemical reactions in biology while opening up the field of time-resolved structural studies of proteins beyond a handful of naturally occurring light-driven systems.

Fields of science (EuroSciVoc)

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Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-ADG - Advanced Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2017-ADG

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Host institution

GOETEBORGS UNIVERSITET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 500 000,00
Address
VASAPARKEN
405 30 Goeteborg
Sweden

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Region
Södra Sverige Västsverige Västra Götalands län
Activity type
Higher or Secondary Education Establishments
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 500 000,00

Beneficiaries (1)

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