Cryptochrome magnetoreception: time course of photoactivation from non-equilibrium coarse-grained molecular dynamics DOI Creative Commons
Jessica L. Ramsay, Fabian Schuhmann, Ilia A. Solov’yov

et al.

Computational and Structural Biotechnology Journal, Journal Year: 2024, Volume and Issue: 26, P. 58 - 69

Published: Nov. 10, 2024

Magnetoreception, the ability to sense magnetic fields, is widespread in animals but remains poorly understood. The leading model links this migratory birds photo-activation of protein cryptochrome. Magnetic information thought induce structural changes cryptochrome via a transient radical pair intermediate. This signal transduction pathway has been subject previous all-atom molecular dynamics (MD) simulations, insights were limited short timescales and equilibrium structures. To address this, we developed non-equilibrium coarse-grained MD simulation approach, exploring cryptochrome's photo-reduction over 20 replicates µs each. Our results revealed significant across protein, with an overall time constant 3 µs. C-terminal (CT) region responded on timescale 4.7 µs, followed by EEE-motif, while phosphate binding loop (PBL) showed slower (9 µs). Network analysis highlighted direct pathways connecting tryptophan tetrad CT, distant involving EEE PBL regions. CT-dynamics are significantly impacted rearrangement residues central electron transfer chain. findings underscore importance considering longer when studying magnetoreception highlight potential simulations as powerful tool unravel photoactivation reactions.

Language: Английский

Adaptive evolution and loss of a putative magnetoreceptor in passerines DOI Creative Commons
Corinna Langebrake, Georg Manthey, Anders Frederiksen

et al.

Proceedings of the Royal Society B Biological Sciences, Journal Year: 2024, Volume and Issue: 291(2016)

Published: Feb. 7, 2024

Migratory birds possess remarkable accuracy in orientation and navigation, which involves various compass systems including the magnetic compass. Identifying primary magnetosensor remains a fundamental open question. Cryptochromes (Cry) have been shown to be magnetically sensitive, Cry4a from migratory songbird seems show enhanced sensitivity vitro compared resident species. We investigate Cry their potential involvement magnetoreception phylogenetic framework, integrating molecular evolutionary analyses with protein dynamics modelling. Our analysis is based on 363 bird genomes identifies different selection regimes passerines. that characterized by strong positive high variability, typical characteristics of sensor proteins. identify key sites are likely facilitated evolution an optimized sensory for night-time songbirds. Additionally, we Cry4 was lost hummingbirds, parrots Tyranni (Suboscines), thus identified gene deletion, might facilitate testing function birds. In contrast, other avian (Cry1 Cry2) were highly conserved across all species, indicating basal, non-sensory functions. results support specialization or functional differentiation songbirds could magnetosensation.

Language: Английский

Citations

9
European Robin Cryptochrome-4a Associates with Lipid Bilayers in an Ordered Manner, Fulfilling a Molecular-Level Condition for Magnetoreception DOI Creative Commons
Marta Majewska, Maja Hanić, Rabea Bartölke

et al.

ACS Chemical Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

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

Language: Английский

Citations

0
Full‐Length Cryptochrome 1 in the Outer Segments of the Retinal Blue Cone Photoreceptors in Humans and Great Apes Suggests a Role Beyond Transcriptional Repression DOI Creative Commons
Rabea Bartölke, Christine Nießner, Katja Reinhard

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(8)

Published: April 25, 2025

ABSTRACT Mammalian cryptochrome 1 (CRY1) is a central player in the circadian transcription‐translation feedback loop, crucial for maintaining roughly 24‐h rhythm. CRY1 was suggested to also function as blue‐light photoreceptor humans and has been found be expressed at mRNA level various cell types of inner retina. However, attempts detect protein human retina have remained unsuccessful so far. Using C‐terminal specific antibodies recognizing full‐length protein, we consistently detected selective labeling outer segments short wavelength‐sensitive (SWS1, “blue”) cone cells across human, bonobo, gorilla retinae. No other retinal were stained, which contrast what would expected ubiquitous clock protein. Subcellular fractionation experiments transfected HEK using antibody located cytosol membrane fractions. Our findings indicate that several different functions including least one nonclock function. results raise likely possibility versions exist humans. We suggest truncation tail, maybe degrees, may affect localization CRY1.

Language: Английский

Citations

0
Migratory birds can extract positional information from magnetic inclination and magnetic declination alone DOI Creative Commons
Florian Packmor, Dmitry Kishkinev, Thomas Zechmeister

et al.

Proceedings of the Royal Society B Biological Sciences, Journal Year: 2024, Volume and Issue: 291(2034)

Published: Nov. 1, 2024

Migratory birds are able to navigate over great distances with remarkable accuracy. The mechanism they use achieve this feat is thought involve two distinct steps: locating their position (the ‘map’) and heading towards the direction determined ‘compass’). For decades, map-and-compass concept has shaped our perception of navigation in animals, although nature map remains debated. However, some recent studies suggest involvement Earth’s magnetic field step. Here, we tested whether migratory songbirds, Eurasian reed warblers ( Acrocephalus scirpaceus ), can determine based on components that also associated finding, i.e. inclination declination. During a virtual displacement experiment, were exposed altered declination values would indicate from natural corridor, but total intensity remained unchanged, creating spatial mismatch between these components. response was change birds’ consistent compensatory re-orientation. This suggests extract positional as well directional information cues, even when conflict another component field. It be seen for navigation.

Language: Английский

Citations

2
Comparison of retinol binding protein 1 with cone specific G-protein as putative effector molecules in cryptochrome signalling DOI Creative Commons
Chad Yee, Rabea Bartölke,

Katharina Görtemaker

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 16, 2024

Abstract Vision and magnetoreception in navigating songbirds are strongly connected as recent findings link a light dependent radical-pair mechanism cryptochrome proteins to signalling pathways cone photoreceptor cells. A previous yeast-two-hybrid screening approach identified six putative candidate showing binding type 4a. So far, only the interaction of specific G-protein transducin α-subunit was investigated more detail. In present study, we compare features with those another from screen, cellular retinol protein. Purified recombinant European robin protein bound high affinity, displaying an EC 50 less than 5 nM, thereby demonstrating its functional state. We applied surface plasmon resonance Förster transfer analysis test for interactions between absence retinol, observed no robust events, which contrasts strong 4a α-subunit. conclude that is unlikely be involved primary magnetosensory cascade.

Language: Английский

Citations

1
European Robin Cryptochrome-4a Associates with Lipid Bilayers in an Ordered Manner, Fulfilling a Molecular-Level Condition for Magnetoreception DOI Creative Commons
Marta Majewska, Maja Hanić, Rabea Bartölke

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 23, 2024

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

Language: Английский

Citations

0
Comparison of retinol binding protein 1 with cone specific G-protein as putative effector molecules in cryptochrome signalling DOI Open Access
Chad Yee, Rabea Bartölke,

Katharina Görtemaker

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 27, 2024

Abstract Vision and magnetoreception in navigating songbirds are strongly connected as recent findings link a light dependent radical-pair mechanism cryptochrome proteins to signalling pathways cone photoreceptor cells. A previous yeast-two-hybrid screening approach identified six putative candidate showing binding type 4a. So far, only the interaction of specific G-protein transducin α-subunit was investigated more detail. In present study, we compare features with those another from screen, cellular retinol protein. Purified recombinant European robin protein bound high affinity, displaying an EC 50 less than 5 nM, thereby demonstrating its functional state. We applied surface plasmon resonance Förster transfer analysis test for interactions between absence retinol, observed no robust events, which contrasts strong 4a α-subunit. conclude that is unlikely be involved primary magnetosensory cascade.

Language: Английский

Citations

0
Full-length Cryptochrome 1 in the outer segments of the retinal blue cone photoreceptors in humans and great apes suggests a role beyond transcriptional repression DOI Open Access
Rabea Bartölke, Christine Nießner, Katja Reinhard

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 11, 2024

Abstract Mammalian cryptochrome 1 (CRY1) is a central player in the circadian transcription-translation feedback loop, crucial for maintaining roughly 24-hour rhythm. CRY1 was suggested to also function as blue-light photoreceptor humans and has been found be expressed at mRNA level various cell types of inner retina. However, attempts detect protein human retina have remained unsuccessful so far. Using C-terminal specific antibodies recognizing full-length protein, we consistently detected selective labelling outer segments short wavelength-sensitive (SWS1, “blue”) cone cells across human, bonobo, gorilla retinae. No other retinal were stained, which contrast what would expected ubiquitous clock protein. Subcellular fractionation experiments transfected HEK using antibody located cytosol membrane fractions. Our findings indicate that several different functions including least one non-clock function. results raise likely possibility versions exists humans. We suggest truncation tail, maybe degrees, may affect localization CRY1.

Language: Английский

Citations

0
Cryptochrome magnetoreception: time course of photoactivation from non-equilibrium coarse-grained molecular dynamics DOI Creative Commons
Jessica L. Ramsay, Fabian Schuhmann, Ilia A. Solov’yov

et al.

Computational and Structural Biotechnology Journal, Journal Year: 2024, Volume and Issue: 26, P. 58 - 69

Published: Nov. 10, 2024

Magnetoreception, the ability to sense magnetic fields, is widespread in animals but remains poorly understood. The leading model links this migratory birds photo-activation of protein cryptochrome. Magnetic information thought induce structural changes cryptochrome via a transient radical pair intermediate. This signal transduction pathway has been subject previous all-atom molecular dynamics (MD) simulations, insights were limited short timescales and equilibrium structures. To address this, we developed non-equilibrium coarse-grained MD simulation approach, exploring cryptochrome's photo-reduction over 20 replicates µs each. Our results revealed significant across protein, with an overall time constant 3 µs. C-terminal (CT) region responded on timescale 4.7 µs, followed by EEE-motif, while phosphate binding loop (PBL) showed slower (9 µs). Network analysis highlighted direct pathways connecting tryptophan tetrad CT, distant involving EEE PBL regions. CT-dynamics are significantly impacted rearrangement residues central electron transfer chain. findings underscore importance considering longer when studying magnetoreception highlight potential simulations as powerful tool unravel photoactivation reactions.

Language: Английский

Citations

0