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Decoding Structural Dynamics of Charge Transfer in Avian Cryptochromes by Time-Resolved Crystallography

Project description

How proteins structurally adapt in charge transfer reactions

Proteins play a key role in charge transfer, which is crucial for functions including photosynthesis and DNA repair. Despite their significance, little is known about how proteins structurally adapt during these change transfer reactions. With the support of the Marie Skłodowska-Curie Actions programme, the CRY TRSX project will focus on cryptochromes – proteins linked to magnetoreception in birds – to explore their structural changes during charge transfer. Using X-ray free-electron lasers, researchers will compare two cryptochromes: one from migratory robins, and another from non-migratory pigeons. By studying their differences, the team should help uncover how structural adaptations stabilise charge transfer states and enable magnetic sensing. The proposed research could transform understanding of charge transfer and reveal how evolution has optimised cryptochromes for their unique biological functions.

Objective

Charge transfer is crucial in many biological processes, including photosynthesis, respiration, and DNA repair. While the kinetics of charge transfer are well studied, the associated protein structural dynamics that guide these reactions remain largely unexplored. This proposal aims to uncover, for the first time, the protein structural rearrangements that occur during charge transfer events, with a particular focus on avian cryptochromes involved in magnetoreception.
Our primary objective is to reveal the structural response of two cryptochromes during charge transfer events using cutting-edge time-resolved serial crystallography (SX) at X-ray free-electron lasers (XFEL) facilities. We intend to elucidate the structure and dynamics of the radical pair state in non-magnetoactive ClCRY4 from non-migratory pigeon (Columba livia) (Objective 1) and magnetoactive ErCRY4 from night-migratory European robin (Erithacus rubecula) (Objective 2). Through comparative analysis of the two samples, we aim to identify the structural adaptations that correlate with their differing biological responses to magnetic fields.
We hypothesize that highly directed structural rearrangements in proteins occur for stabilizing charge transfer states. This contrast current textbook knowledge. By focusing on radical pair states in cryptochromes, our comparative study between ErCRY4 and ClCRY4 will enable us to determine whether and how structural adaptations are aligned with their biological functions.
This research is poised to make a significant impact in charge transfer theory, and will provide the first structural basis to understand magnetosensing in crpytochromes. We anticipate establishing a new paradigm in which protein structural fluctuations actively drive charge transfer reactions, and may reveal evolutionary optimizations in how cryptchromes have facilitated this for optimization of their sensing functions.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

UPPSALA UNIVERSITET
Net EU contribution
€ 236 340,00
Address
VON KRAEMERS ALLE 4
751 05 Uppsala
Sweden
Region
Östra Sverige Östra Mellansverige Uppsala län
Activity type
Higher or Secondary Education Establishments
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Total cost
No data