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PreprintCited by 12Electromagnetic Fields and Biological EffectsLipid Membrane Structure and BehaviorElectron Spin Resonance Studies

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European Robin Cryptochrome-4a Associates with Lipid Bilayers in an Ordered Manner, Fulfilling a Molecular-Level Condition for Magnetoreception

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Majewska, Marta, Hanić, Maja, Bartölke, Rabea, Schmidt, Jessica, Mouritsen, Henrik, Koch, Karl-Wilhelm, Solov’yov, Ilia A., Brand, Izabella·2024·ACS Chemical Biology
DOI 10.1101/2024.07.20.604329PMC PMC11934094

Preprint — published as 10.1021/acschembio.4c00576

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Abstract

Since the middle of the 20th century, long-distance avian migration has been known to rely partly on the geomagnetic field. However, the underlying sensory mechanism is still not fully understood. Cryptochrome 4a (ErCry4a), found in European Robin ( Erithacus rubecula ), a night-migratory songbird has been suggested to be a magnetic sensory molecule. It is sensitive to external magnetic fields via the so-called radical-pair mechanism. ErCry4a is primarily located in the outer segments of the double cone photoreceptor cells in the eye, which contain stacked and highly ordered membranes that could facilitate the anisotropic attachment of ErCry4a needed for magnetic compass sensing. Here, we investigate possible interactions of ErCry4a with a model membrane that mimics the lipid composition of outer segments of vertebrate photoreceptor cells by using experimental and computational approaches. Experimental results show that the attachment of ErCry4a to the membrane could be controlled by the physical state of lipid molecules (average area per lipid) in the outer leaflet of the lipid bilayer. Furthermore, polarization modulation infrared reflection absorption spectroscopy allowed us to determine the conformation, motional freedom, and average orientation of the α- helices in ErCry4a in a membrane-associated state. Atomistic molecular dynamics studies supported the experimental results. A ∼1000 kcal mol −1 decrease in the interaction energy as a result of ErCry4a membrane binding was determined compared to cases where no protein binding to the membrane occurred. At the molecular level, the binding seems to involve negatively charged carboxylate groups of the phosphoserine lipids and the C-terminal residues of ErCry4a. Our study reveals a potential direct interaction of ErCry4a with the lipid membrane and discusses how this binding could be an essential step for ErCry4a to propagate a magnetic signal further and thus fulfill a role as a magnetoreceptor.

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Research works printed but not linked: 109

  1. 10.1038/s41586-018-0176-1 · DOI
  2. 10.1038/364525a0 · DOI
  3. 10.1016/j.cub.2017.12.003 · DOI · Paper page
  4. 2020, A novel isoform of cryptochrome 4 (Cry4b) is expressed in the retina of a night-migratory songbird, Sci Rep-Uk, 10, 15794, 10.1038/s41598-020-72579-2 · DOI
  5. 2012, The magnetic retina: light-dependent and trigeminal magnetoreception in migratory birds, Curr. Opin. Neurol, 22, 343, 10.1016/j.conb.2012.01.005 · DOI
  6. 10.1038/nature08528 · DOI
  7. 10.1073/pnas.0409575102 · DOI
  8. 2022, Morphology, biochemistry and connectivity of Cluster N and the hippocampal formation in a migratory bird, Brain Struct. Funct, 227, 2731, 10.1007/s00429-022-02566-y · DOI
  9. 10.1038/nature02534 · DOI · Paper page
  10. 10.1016/j.bpj.2017.07.031 · DOI
  11. Schwarze, S. ; Schneider, N.-L. ; Reichl, T. ; Dreyer, D. ; Lefeldt, N. ; Engels, S. ; Baker, N. ; Hore, P. ; Mouritsen, H . Weak broadband electromagnetic fields are more disruptive to magnetic compass orientation in a night-migratory songbird (Erithacus rubecula) than strong narrow-band fields. Front. Behav. Neurosci. 2016, 10, 55. · DOI
  12. 10.1038/nature13290 · DOI · Paper page
  13. 10.1098/rsif.2017.0364 · DOI
  14. Kobylkov, D. ; Wynn, J. ; Winklhofer, M. ; Chetverikova, R. ; Xu, J. ; Hiscock, H. ; Hore, P. J. ; Mouritsen, H . Electromagnetic 0.1–100 kHz noise does not disrupt orientation in a night-migrating songbird implying a spin coherence lifetime of less than 10 µs. J R Soc Interface 2019, 16, 20190716. · DOI
  15. 2022, Broadband 75–85 MHz radiofrequency fields disrupt magnetic compass orientation in night-migratory songbirds consistent with a flavin-based radical pair magnetoreceptor, J. Comp. Physiol. A, 208, 97, 10.1007/s00359-021-01537-8 · DOI
  16. 2023, Upper bound for broadband radiofrequency field disruption of magnetic compass orientation in night- migratory songbirds, Proc. Natl. Acad. Sci, 120, e2301153120, 10.1073/pnas.2301153120 · DOI
  17. 2021, Navigation of migratory songbirds: a quantum magnetic compass sensor, Neuroforum, 27, 141, 10.1515/nf-2021-0005 · DOI
  18. 10.1146/annurev-biophys-032116-094545 · DOI · Paper page
  19. 10.1016/j.bpj.2010.03.053 · DOI
  20. 10.1016/S0006-3495(00)76629-X · DOI · Paper page
  21. 2022, Effects of Dynamical Degrees of Freedom on Magnetic Compass Sensitivity: A Comparison of Plant and Avian Cryptochromes, J. Am. Chem. Soc, 144, 22902, 10.1021/jacs.2c06233 · DOI
  22. 10.1073/pnas.1600341113 · DOI · Paper page
  23. 2023, Tracking the Electron Transfer Cascade in European Robin Cryptochrome 4 Mutants, J. Am. Chem. Soc, 145, 11566, 10.1021/jacs.3c00442 · DOI
  24. 2012, Reaction kinetics and mechanism of magnetic field effects in cryptochrome, J. Phys. Chem. B, 116, 1089, 10.1021/jp209508y · DOI
  25. 2014, Separation of photo-induced radical pair in cryptochrome to a functionally critical distance, Sci Rep-Uk, 4, 3845, 10.1038/srep03845 · DOI
  26. 2016, Electron spin relaxation can enhance the performance of a cryptochrome-based magnetic compass sensor, New J. Phys, 18, 063007, 10.1088/1367-2630/18/6/063007 · DOI
  27. 2021, Cryptochrome magnetoreception: four tryptophans could be better than three, J R Soc Interface, 18, 20210601, 10.1098/rsif.2021.0601 · DOI
  28. 2019, Navigating at night: fundamental limits on the sensitivity of radical pair magnetoreception under dim light, Q. Rev. Biophys, 52, e9, 10.1017/S0033583519000076 · DOI
  29. 10.1098/rsif.2009.0399.focus · DOI
  30. 1978, A biomagnetic sensory mechanism based on magnetic field modulated coherent electron spin motion, Z. Phys. Chem, 111, 1, 10.1524/zpch.1978.111.1.001 · DOI · Paper page
  31. 2016, Localisation of the Putative Magnetoreceptive Protein Cryptochrome 1b in the Retinae of Migratory Birds and Homing Pigeons, PLoS One, 11, e0147819, 10.1371/journal.pone.0147819 · DOI
  32. 2021, Cryptochrome 1a localisation in light- and dark-adapted retinae of several migratory and non-migratory bird species: no signs of light-dependent activation, Ethol. Ecol. Evol, 33, 248, 10.1080/03949370.2020.1870571 · DOI
  33. 2022, Double cones in the avian retina form an oriented mosaic which might facilitate magnetoreception and/or polarized light sensing, J R Soc Interface, 19, 20210877, 10.1098/rsif.2021.0877 · DOI
  34. 2022, Localisation of cryptochrome 2 in the avian retina, J. Comp. Physiol. A, 208, 69, 10.1007/s00359-021-01506-1 · DOI
  35. Hochstoeger, T. ; Al Said, T. ; Maestre, D. ; Walter, F. ; Vilceanu, A. ; Pedron, M. ; Cushion, T. D. ; Snider, W. ; Nimpf, S. ; Nordmann, G. C. ; Landler, L. ; Edelman, N. ; Kruppa, L. ; Dürnberger, G. ; Mechtler, K. ; Schuechner, S. ; Ogris, E. ; Malkemper, E. P. ; Weber, S. ; Schleicher, E. ; Keays, D. A . The biophysical, molecular, and anatomical landscape of pigeon CRY4: A candidate light-based quantal magnetosensor. Sci. Adv. 2020, 6, eabb9110. · DOI
  36. 2004, Retinal cryptochrome in a migratory passerine bird: a possible transducer for the avian magnetic compass, Sci. Nat, 91, 585, 10.1007/s00114-004-0578-9 · DOI · Paper page
  37. 10.1073/pnas.0405968101 · DOI
  38. 10.1371/journal.pone.0020091 · DOI
  39. 10.1371/journal.pone.0150377 · DOI
  40. 10.1038/s41586-021-03618-9 · DOI
  41. 2020, Structural explanations of flavin adenine dinucleotide binding in Drosophila melanogaster cryptochrome, J. Phys. Chem. Lett, 11, 3866, 10.1021/acs.jpclett.0c00625 · DOI
  42. 2017, Vertebrate cryptochromes are vestigial flavoproteins, Sci Rep-Uk, 7, 1
  43. 10.1126/science.286.5440.768 · DOI
  44. Langebrake, C. ; Manthey, G. ; Frederiksen, A. ; Ramos, J. S. L. ; Dutheil, J. Y. ; Chetverikova, R. ; Solov’yov, I. A. ; Mouritsen, H. ; Liedvogel, M . Adaptive evolution and loss of a putative magnetoreceptor in passerines. Proc. R. Soc. B 2024, 291, 20232308. · DOI
  45. 10.1073/pnas.1907875116 · DOI
  46. 10.1111/j.1460-9568.2010.07311.x · DOI
  47. Wu, H. J. ; Scholten, A. ; Einwich, A. ; Mouritsen, H. ; Koch, K. W . Protein-protein interaction of the putative magnetoreceptor cryptochrome 4 expressed in the avian retina. Sci Rep-Uk 2020, 10 (1), . · DOI
  48. 2021, The secrets of cryptochromes: photoreceptors, clock proteins, and magnetic sensors, Neuroforum, 27, 151, 10.1515/nf-2021-0006 · DOI
  49. Gortemaker, K. ; Yee, C. ; Bartolke, R. ; Behrmann, H. ; Voss, J. O. ; Schmidt, J. ; Xu, J. J. ; Solovyeva, V. ; Leberecht, B. ; Behrmann, E. ; Mouritsen, H. ; Koch, K. W . Direct Interaction of Avian Cryptochrome 4 with a Cone Specific G-Protein. Cells-Basel 2022, 11 (13), . · DOI
  50. 2013, Prediction of lipid-binding regions in cytoplasmic and extracellular loops of membrane proteins as exemplified by potein translocation membrane proteins, J. Membr. Biol, 246, 21, 10.1007/s00232-012-9498-3 · DOI
  51. 2006, Roles of bilayer material properties in function and distribution of membrane proteins, Annu. Rev. Biophys, 35, 177, 10.1146/annurev.biophys.35.040405.102022 · DOI
  52. 2021, Membrane binding properties of the C-terminal segment of retinol dehydrogenase 8, Biochim.Biophys. Acta, 1863, 183601
  53. 10.1021/ja064093h · DOI
  54. 2009, Lipid metabolism in vertebrate retinal rod outer segments, Prog. Lipid Res, 39, 315
  55. Martin, R. E. ; Elliott, M. H. ; Brush, R. S. ; Anderson, R. E . Detailed characterization of the lipid composition of detergent-resistant membranes from photoreceptor rod outer segment membranes. IOVS 2005, 46 (4), . · DOI
  56. 1974, Phospholipids of the cone-rich chicken retina and its photoreceptor outer segment membranes, Biochim.Biophys. Acta, 369, 269, 10.1016/0005-2760(74)90141-6 · DOI
  57. 2015, Atomic force microscopy and electrochemical studies of melittin action on lipid bilayers supported on gold electrodes, Electrochim. Acta, 162, 53, 10.1016/j.electacta.2014.10.039 · DOI
  58. 10.1021/acs.biochem.6b01063 · DOI
  59. 10.1016/j.plipres.2011.03.002 · DOI
  60. 2021, Nano-scale resolution of native retinal rod disk membranes reveals differences in lipid composition, J. Cell Biol, 8, e202101063
  61. 10.1016/j.bbabio.2007.06.004 · DOI · Paper page
  62. Brand, I. Application of Polarization Modulation Infrared Reflection Absorption Spectroscopy in Electrochemistry; Springer Nature, 2020. · DOI
  63. Kycia, A. H. ; Su, Z. F. ; Brosseau, C. L. ; Lipkowski, J. In situ PM-IRRAS studies of biomimetic membranes supported at a gold electrode surface. In Vibration spectroscopy at electrified interfaces, Wieckowski, A. , Korzeniewski, C. , Braunschweig, B. Eds.; Wiley, 2013; pp 345–417. · DOI
  64. 10.1063/1.444442 · DOI
  65. 10.1021/bi00820a019 · DOI
  66. 10.1021/bi970938d · DOI
  67. 1960, Use of glass electodes to measure acidities in deuterium oxide, J. Phys. Chem. B, 64, 188, 10.1021/j100830a521 · DOI
  68. 10.1002/jcc.20289 · DOI · Paper page
  69. 10.1016/0263-7855(96)00018-5 · DOI · Paper page
  70. 10.1002/jcc.23702 · DOI
  71. 10.1371/journal.pone.0000880 · DOI
  72. 2018, CHARMM-GUI membrane builder for complex biological membrane simulations with glycolipids and lipoglycans, J. Chem. Theory Comput, 15, 775
  73. 1999, NAMD2: greater scalability for parallel molecular dynamics, J. Comput. Phys, 151, 283, 10.1006/jcph.1999.6201 · DOI
  74. Phillips, J. C. ; Hardy, D. J. ; Maia, J. D. C. ; Stone, J. E. ; Ribeiro, J. V. ; Bernardi, R. C. ; Buch, R. ; Fiorin, G. ; Henin, J. ; Jiang, W. ; McGreevy, R. ; Melo, M. C. R. ; Radak, B. K. ; Skeel, R. D. ; Singharoy, A. ; Wang, Y. ; Roux, B. ; Aksimentiev, A. ; Luthey- Schulten, Z. ; Kale, L. V. ; Schulten, K. ; Chipot, C. ; Tajkhorshid, E . Scalable molecular dynamics on CPU and GPU architectures with NAMD. J. Chem. Phys. 2020, 153 (4), · DOI
  75. 2019, Introducing VIKING: A novel online platform for multiscale modeling, ACS Omega, 5, 1254
  76. 10.1002/jcc.23354 · DOI
  77. 10.1529/biophysj.105.078154 · DOI
  78. 10.1002/(SICI)1096-987X(20000130)21:2<86::AID-JCC2>3.0.CO;2-G · DOI
  79. 10.1021/ja3074819 · DOI
  80. 10.1021/ja510550g · DOI
  81. 10.1523/JNEUROSCI.2495-20.2021 · DOI
  82. 2021, Exploring Post-activation Conformational Changes in Pigeon Cryptochrome 4, J. Phys. Chem. B, 125, 9652, 10.1021/acs.jpcb.1c02795 · DOI
  83. 2022, Computational Reconstruction and Analysis of Structural Models of Avian Cryptochrome 4, J. Phys. Chem. B, 126, 4623, 10.1021/acs.jpcb.2c00878 · DOI
  84. 10.1063/1.464397 · DOI
  85. 10.1002/prot.340230412 · DOI
  86. 2014, VMD-SS: A graphical user interface plug-in to calculate the protein secondary structure in VMD program, Bioinform, 10, 548, 10.6026/97320630010548 · DOI
  87. 10.1021/ACS.JCTC.1C00708/ · DOI
  88. 1984, Lateral chain packing in lipids and membranes, J. Lipid Res, 25, 1490, 10.1016/S0022-2275(20)34422-9 · DOI
  89. Davies, J. T. ; Rideal, E. K. The Physics of Surfaces. In Interfacial phenomena, Davies, J. T. , Rideal, E. K. Eds.; Elsevier, 1961; pp 1–55. · DOI
  90. 10.1016/S0305-0491(98)10079-2 · DOI
  91. 1999, Structure and phase transitions in Langmuir monolayers, Rev.Mod. Phys, 71, 779, 10.1103/RevModPhys.71.779 · DOI
  92. 10.1021/la104097n · DOI
  93. 2020, Mechanisms of light-induced deformations in photoreceptors, Biophys. J, 119, 1481, 10.1016/j.bpj.2020.09.005 · DOI
  94. 10.1073/pnas.1920039117 · DOI
  95. 10.1021/bi00720a024 · DOI
  96. 2016, Physicochemical studies on orientation and conformation of a new bacteriocin BacSp222 in a planar phospholipid bilayer, Langmuir, 32, 5653, 10.1021/acs.langmuir.5b04741 · DOI
  97. 2018, Binding of a myristoylated protein to the lipid membrane influenced by interactions with the polar head group region, Langmuir, 34, 14022, 10.1021/acs.langmuir.8b02265 · DOI
  98. 1962, Infrared dichroism and molecular conformation of a-form poly-g-benzym- L-glutamate, J. Polym. Sci, 59, 139, 10.1002/pol.1962.1205916712 · DOI
  99. 10.1016/S0006-3495(00)76795-6 · DOI
  100. 10.1021/ja01464a042 · DOI
  101. 2010, Building biomimetic membrane at a gold electrode surface, Phys. Chem. Chem. Phys, 12, 13874, 10.1039/c0cp00658k · DOI
  102. 10.1021/bi047545g · DOI
  103. 10.1074/jbc.M112.395731 · DOI
  104. Berntsson, O. ; Rodriguez, R. ; Henry, L. ; Panman, M. R. ; Hughes, A. J. ; Einholz, C. ; Weber, S. ; Ihalainen, J. A. ; Henning, R. ; Kosheleva, I. ; Schleicher, E. ; Westenhoff, S . Photoactivation of Drosophila melanogaster cryptochrome through sequential conformational transitions. Sci. Adv. 2019, 5 (7), eaaw1531. · DOI
  105. 10.1016/S0014-4835(03)00151-9 · DOI
  106. 10.1073/pnas.1212317110 · DOI
  107. Israelachvili, J. Intermolecular and Surface Forces; Academic Press, 1992.
  108. 2010, Molecular volumes of phospholipids and glycolipids in membranes, Chem. Phys. Lipids, 163, 667, 10.1016/j.chemphyslip.2010.06.005 · DOI
  109. 2019, Physical properties of model biological lipid bilayers: insights from all-atom molecular dynamics simulations, J. Mol. Model, 76, 71

Metadata

Authors
Majewska, M., Hanić, M., Bartölke, R., Schmidt, J., Mouritsen, H., Koch, K.-W., Solov’yov, I. A., & Brand, I.
Affiliations
Carl von Ossietzky Universität Oldenburg (DE)
Corresponding author
  • Solov’yov, Ilia A.
  • Brand, Izabella
ORCID
Venue
ACS Chemical Biology
Publisher
openRxiv
Published
2024-07-23
Volume
20
Issue
3
Pages
592-606
ISSN
1554-8929 (ISSN-L)
DOI
10.1101/2024.07.20.604329
PMC
PMC11934094
OpenAlex
W4407838431
Cited by
12
References
1
Citations by year
2026: 10 · 2025: 2
FWCI
4.52
Type
journal article
Language
en
Open access
Licence
Locations
  • ACS Chemical Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Carl von Ossietzky Universität Oldenburg
  • European Commission (HORIZON2020)
  • Deutsche Forschungsgemeinschaft (GRK1885, TRR386/1 2023, TRR-386, 395940726, SFB 1372, 514664767, 216581600, TRR386/1)
  • Volkswagen Foundation (SFB-1372, 395940726, GRK1885)
  • Bundesministerium für Bildung und Forschung
  • Niedersächsisches Ministerium für Wissenschaft und Kultur
  • H2020 European Research Council (810002)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Electromagnetic Fields and Biological Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Physical Sciences › Chemistry › Spectroscopy › Electron Spin Resonance Studies
Keywords
European robin, Erithacus rubecula, magnetoreception, bird migration, radical pair mechanism, photoreceptor outer segments, lipid bilayer binding, protein-membrane interactions, area per lipid, alpha-helix orientation, carboxylate groups
MeSH terms
Animals, Lipid Bilayers, Songbirds, Molecular Dynamics Simulation, Cryptochromes, Magnetic Fields

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