Directed Ultrafast Conformational Changes Accompany Electron Transfer in a Photolyase As Resolved by Serial Crystallography

Overview

Journal Nat Chem

Specialty Chemistry

Date 2024 Jan 15

PMID 38225270

Authors

Andrea Cellini

Madan Kumar Shankar

Amke Nimmrich

Leigh Anna Hunt

Leonardo Monrroy

Jennifer Mutisya

Antonia Furrer

Emma V Beale

Melissa Carrillo

Tek Narsingh Malla

Piotr Maj

Lidija Vrhovac

Florian Dworkowski

Claudio Cirelli

Philip J M Johnson

Dmitry Ozerov

Emina A Stojkovic

Leif Hammarstrom

Camila Bacellar

Jorg Standfuss

Michal Maj

Marius Schmidt

Tobias Weinert

Janne A Ihalainen

Weixiao Yuan Wahlgren

Sebastian Westenhoff

Affiliations

Soon will be listed here.

Abstract

Charge-transfer reactions in proteins are important for life, such as in photolyases which repair DNA, but the role of structural dynamics remains unclear. Here, using femtosecond X-ray crystallography, we report the structural changes that take place while electrons transfer along a chain of four conserved tryptophans in the Drosophila melanogaster (6-4) photolyase. At femto- and picosecond delays, photoreduction of the flavin by the first tryptophan causes directed structural responses at a key asparagine, at a conserved salt bridge, and by rearrangements of nearby water molecules. We detect charge-induced structural changes close to the second tryptophan from 1 ps to 20 ps, identifying a nearby methionine as an active participant in the redox chain, and from 20 ps around the fourth tryptophan. The photolyase undergoes highly directed and carefully timed adaptations of its structure. This questions the validity of the linear solvent response approximation in Marcus theory and indicates that evolution has optimized fast protein fluctuations for optimal charge transfer.

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References

Aubert C, Vos M, Mathis P, Eker A, Brettel K . Intraprotein radical transfer during photoactivation of DNA photolyase. Nature. 2000; 405(6786):586-90. DOI: 10.1038/35014644. View

Mouritsen H . Long-distance navigation and magnetoreception in migratory animals. Nature. 2018; 558(7708):50-59. DOI: 10.1038/s41586-018-0176-1. View

Kumar Pal S, Peon J, Zewail A . Biological water at the protein surface: dynamical solvation probed directly with femtosecond resolution. Proc Natl Acad Sci U S A. 2002; 99(4):1763-8. PMC: 122267. DOI: 10.1073/pnas.042697899. View

Qiu W, Kao Y, Zhang L, Yang Y, Wang L, Stites W . Protein surface hydration mapped by site-specific mutations. Proc Natl Acad Sci U S A. 2006; 103(38):13979-84. PMC: 1599899. DOI: 10.1073/pnas.0606235103. View

Cailliez F, Muller P, Firmino T, Pernot P, de la Lande A . Energetics of Photoinduced Charge Migration within the Tryptophan Tetrad of an Animal (6-4) Photolyase. J Am Chem Soc. 2016; 138(6):1904-15. DOI: 10.1021/jacs.5b10938. View

Branden G, Neutze R . Advances and challenges in time-resolved macromolecular crystallography. Science. 2021; 373(6558). DOI: 10.1126/science.aba0954. View

Liebschner D, Afonine P, Baker M, Bunkoczi G, Chen V, Croll T . Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix. Acta Crystallogr D Struct Biol. 2019; 75(Pt 10):861-877. PMC: 6778852. DOI: 10.1107/S2059798319011471. View

Claesson E, Wahlgren W, Takala H, Pandey S, Castillon L, Kuznetsova V . The primary structural photoresponse of phytochrome proteins captured by a femtosecond X-ray laser. Elife. 2020; 9. PMC: 7164956. DOI: 10.7554/eLife.53514. View

Immeln D, Weigel A, Kottke T, Lustres J . Primary events in the blue light sensor plant cryptochrome: intraprotein electron and proton transfer revealed by femtosecond spectroscopy. J Am Chem Soc. 2012; 134(30):12536-46. DOI: 10.1021/ja302121z. View

10.

Liu Z, Tan C, Guo X, Li J, Wang L, Sancar A . Determining complete electron flow in the cofactor photoreduction of oxidized photolyase. Proc Natl Acad Sci U S A. 2013; 110(32):12966-71. PMC: 3740875. DOI: 10.1073/pnas.1311073110. View

11.

Krapf S, Koslowski T, Steinbrecher T . The thermodynamics of charge transfer in DNA photolyase: using thermodynamic integration calculations to analyse the kinetics of electron transfer reactions. Phys Chem Chem Phys. 2010; 12(32):9516-25. DOI: 10.1039/c000876a. View

12.

Kim G, Weiss S, Levine R . Methionine oxidation and reduction in proteins. Biochim Biophys Acta. 2013; 1840(2):901-5. PMC: 3766491. DOI: 10.1016/j.bbagen.2013.04.038. View

13.

Zhang M, Wang L, Zhong D . Photolyase: Dynamics and Mechanisms of Repair of Sun-Induced DNA Damage. Photochem Photobiol. 2016; 93(1):78-92. PMC: 5315619. DOI: 10.1111/php.12695. View

14.

Gray H, Winkler J . Electron transfer in proteins. Annu Rev Biochem. 1996; 65:537-61. DOI: 10.1146/annurev.bi.65.070196.002541. View

15.

Nogly P, Weinert T, James D, Carbajo S, Ozerov D, Furrer A . Retinal isomerization in bacteriorhodopsin captured by a femtosecond x-ray laser. Science. 2018; 361(6398). DOI: 10.1126/science.aat0094. View

16.

Dods R, Bath P, Morozov D, Ahlberg Gagner V, Arnlund D, Luk H . Ultrafast structural changes within a photosynthetic reaction centre. Nature. 2020; 589(7841):310-314. DOI: 10.1038/s41586-020-3000-7. View

17.

Liu Z, Wang L, Zhong D . Dynamics and mechanisms of DNA repair by photolyase. Phys Chem Chem Phys. 2015; 17(18):11933-49. PMC: 4447866. DOI: 10.1039/c4cp05286b. View

18.

Popovic D, Zmiric A, Zaric S, Knapp E . Energetics of radical transfer in DNA photolyase. J Am Chem Soc. 2002; 124(14):3775-82. DOI: 10.1021/ja016249d. View

19.

Cellini A, Shankar M, Wahlgren W, Nimmrich A, Furrer A, James D . Structural basis of the radical pair state in photolyases and cryptochromes. Chem Commun (Camb). 2022; 58(31):4889-4892. PMC: 9008703. DOI: 10.1039/d2cc00376g. View

20.

Babcock G, Wikstrom M . Oxygen activation and the conservation of energy in cell respiration. Nature. 1992; 356(6367):301-9. DOI: 10.1038/356301a0. View