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Currents of Life – Molecular Mechanism of Long-Range Biological Energy Transduction

Objective

Life is powered by a membrane-bound protein machinery that captures chemical and light energy to sustain the cellular energy metabolism. At the molecular level, these processes are catalyzed by energy-transducing enzyme complexes that link proton-coupled electron transfer (PCET) reactions across remarkably large (>300 Å) molecular distances. The Complex I machinery is the largest (>1 MDa) and most intricate PCET enzyme known, initiating electron transport chains across all domains of life. It operates fully reversibly near optimal thermodynamic efficiency, and provides a basis for the energy metabolism. Despite recent advances, the physical
principles of the long-range biological PCET processes remain poorly understood and much debated. This ERC project aims to elucidate the molecular mechanism of long-range PCET reactions in biological energy transduction, with an emphasis on the underlying electrodynamic coupling principles. To address these challenging questions, we develop integrative multi-layered computational methods together with biochemical, biophysical, and structural experiments, allowing us to elucidate how the protein structure and dynamics enable the charge transfer reactions on a broad range of timescales and spatial resolutions. We address the crosstalk between proton- and electron transferring modules in different domains of life to unravel the exact time-ordered molecular principles of biological energy catalysis and to study how electric field effects provide the catalytic properties of these intricate bioenergetic machines. We further engineer the modular enzyme structure to gain functional insights and probe how disease-related mutations perturb the charge transfer reactions. The integrated methodological approach could shift paradigms in our current understanding of enzyme function, with profound implications for chemistry, physics, and biology, and with an ultimate goal to unravel the molecular blueprints of biological energy catalysis.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2025-ADG

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Host institution

STOCKHOLMS 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.

€ 2 494 937,00
Address
UNIVERSITETSVAGEN 10
10691 Stockholm
Sweden

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Region
Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
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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.

No data

Beneficiaries (1)