Dimerization of European Robin Cryptochrome 4a

Homo-dimer formation is important for the function of many proteins. Although dimeric forms of cryptochromes (Cry) have been found by crystallography and were recently observed in vitro for European robin Cry4a, little is known about the dimerisation of avian cryptochromes and the role it could play in the mechanism of magnetic sensing in migratory birds. Here we present a combined experimental and computational investigation of the dimerisation of robin Cry4a resulting from covalent and non-covalent interactions. Experimental studies using native mass spectrometry, mass spectrometric analysis of disulphide bonds, chemical cross-linking and photometric measurements show that disulphide-linked dimers are routinely formed, the most likely cysteines being C317 and C412. Computational modelling and molecular dynamics simulations were used to generate and assess a number of possible dimer structures. The relevance of these findings to the proposed role of Cry4a in avian magnetoreception is discussed.

• Publication year

  2023

• Venue

  bioRxiv

• Publication date

  2023-04-11

• Fields of study

  Biology, Medicine, Chemistry, Environmental Science

• Identifiers
  DOI 10.1101/2023.04.11.536350PMID 37428840PMCID 10364083
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Direct Interaction of Avian Cryptochrome 4 with a Cone Specific G-Protein

  2022cited by this paper
• A Cryptochrome adopts distinct moon- and sunlight states and functions as sun- versus moonlight interpreter in monthly oscillator entrainment

  2022cited by this paper
• On the energetic differences of avian cryptochromes 4 from selected species

  2022cited by this paper
• Double cones in the avian retina form an oriented mosaic which might facilitate magnetoreception and/or polarized light sensing

  2022cited by this paper
• Nuclear polarization effects in cryptochrome-based magnetoreception.

  2021cited by this paper
• Introducing Pep McConst—A user‐friendly peptide modeler for biophysical applications

  2021cited by this paper
• Structural insights into photoactivation of plant Cryptochrome-2

  2021cited by this paper
• Localisation of cryptochrome 2 in the avian retina

  2021cited by this paper
• The expression, localisation and interactome of pigeon CRY2

  2021cited by this paper
• Exploring Post-activation Conformational Changes in Pigeon Cryptochrome 4.

  2021cited by this paper
• Magnetic sensitivity of cryptochrome 4 from a migratory songbird

  2021cited by this paper
• Cryptochrome 1a localisation in light- and dark-adapted retinae of several migratory and non-migratory bird species: no signs of light-dependent activation

  2021cited by this paper
• Tuning flavin environment to detect and control light-induced conformational switching in Drosophila cryptochrome

  2021cited by this paper
• Protein-protein interaction of the putative magnetoreceptor cryptochrome 4 expressed in the avian retina

  2020cited by this paper
• A novel isoform of cryptochrome 4 (Cry4b) is expressed in the retina of a night-migratory songbird

  2020cited by this paper
• Scalable molecular dynamics on CPU and GPU architectures with NAMD.

  2020cited by this paper
• The oligomeric structures of plant cryptochromes

  2020cited by this paper
• Isoform-selective regulation of mammalian cryptochromes

  2020cited by this paper
• The tail of cryptochromes: an intrinsically disordered cog within the mammalian circadian clock

  2020cited by this paper
• The DASH-type Cryptochrome from the Fungus Mucor circinelloides Is a Canonical CPD-Photolyase.

  2020cited by this paper
• Structural insights into photoactivation of plant Cryptochrome-2

  2020cited by this paper
• Mechanisms of Cryptochrome-Mediated Photoresponses in Plants.

  2020cited by this paper
• The biophysical, molecular, and anatomical landscape of pigeon CRY4: A candidate light-based quantal magnetosensor

  2020cited by this paper
• Introducing VIKING: A Novel Online Platform for Multiscale Modeling

  2019cited by this paper
• Chemical and structural analysis of a photoactive vertebrate cryptochrome from pigeon

  2019cited by this paper
• Quantitative mass imaging of single biological macromolecules

  2018cited by this paper
• Structural and mechanistic aspects of S-S bonds in the thioredoxin-like family of proteins

  2018cited by this paper
• Quantitative mass imaging of single molecules

  2018cited by this paper
• Molecular dynamics simulations disclose early stages of the photo-activation of cryptochrome 4

  2018cited by this paper
• A cross-linking/mass spectrometry workflow based on MS-cleavable cross-linkers and the MeroX software for studying protein structures and protein–protein interactions

  2018cited by this paper
• Double-Cone Localization and Seasonal Expression Pattern Suggest a Role in Magnetoreception for European Robin Cryptochrome 4.

  2018cited by this paper
• Animal Cryptochromes: Divergent Roles in Light Perception, Circadian Timekeeping and Beyond

  2017cited by this paper
• Phylogenetic and Functional Classification of the Photolyase/Cryptochrome Family

  2017cited by this paper
• Optogenetic protein clustering through fluorescent protein tagging and extension of CRY2

  2017cited by this paper
• Seasonally Changing Cryptochrome 1b Expression in the Retinal Ganglion Cells of a Migrating Passerine Bird

  2016cited by this paper
• Protein Dimerization And Oligomerization In Biology

  2016cited by this paper
• Localisation of the Putative Magnetoreceptive Protein Cryptochrome 1b in the Retinae of Migratory Birds and Homing Pigeons

  2016cited by this paper
• The Radical-Pair Mechanism of Magnetoreception.

  2016cited by this paper
• Quantifying electron transfer reactions in biological systems: what interactions play the major role?

  2015cited by this paper
• I-TASSER server: new development for protein structure and function predictions

  2015cited by this paper
• Solvent driving force ensures fast formation of a persistent and well-separated radical pair in plant cryptochrome.

  2015cited by this paper
• ZDOCK server: interactive docking prediction of protein-protein complexes and symmetric multimers

  2014cited by this paper
• Automated Assignment of MS/MS Cleavable Cross-Links in Protein 3D-Structure Analysis

  2014cited by this paper
• A review of methods available to estimate solvent-accessible surface areas of soluble proteins in the folded and unfolded states.

  2014cited by this paper
• Separation of photo-induced radical pair in cryptochrome to a functionally critical distance

  2014cited by this paper
• The I-TASSER Suite: protein structure and function prediction

  2014cited by this paper
• Interaction of circadian clock proteins CRY1 and PER2 is modulated by zinc binding and disulfide bond formation.

  2014cited by this paper
• Structures of Drosophila cryptochrome and mouse cryptochrome1 provide insight into circadian function.

  2013cited by this paper
• Updated structure of Drosophila cryptochrome

  2013cited by this paper
• Light-dependent Structural Change of Chicken Retinal Cryptochrome4*

  2012cited by this paper
• Protein Dimerization and Oligomerization in Biology

  2012cited by this paper
• Magnetically sensitive light-induced reactions in cryptochrome are consistent with its proposed role as a magnetoreceptor

  2012cited by this paper
• Decrypting cryptochrome: revealing the molecular identity of the photoactivation reaction.

  2012cited by this paper
• Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone φ, ψ and side-chain χ(1) and χ(2) dihedral angles.

  2012cited by this paper
• The cryptochromes: blue light photoreceptors in plants and animals.

  2011cited by this paper
• Avian Ultraviolet/Violet Cones Identified as Probable Magnetoreceptors

  2011cited by this paper
• Light-induced conformational changes in full-length Arabidopsis thaliana cryptochrome.

  2011cited by this paper
• Accelerating Protein Docking in ZDOCK Using an Advanced 3D Convolution Library

  2011cited by this paper
• Development of a Novel Cross-linking Strategy for Fast and Accurate Identification of Cross-linked Peptides of Protein Complexes*

  2010cited by this paper
• Production of glycoprotein-deleted rabies viruses for monosynaptic tracing and high-level gene expression in neurons

  2010cited by this paper
• The Cryptochrome Blue Light Receptors

  2010cited by this paper
• I-TASSER: a unified platform for automated protein structure and function prediction

  2010cited by this paper
• Cleavable cross-linker for protein structure analysis: reliable identification of cross-linking products by tandem MS.

  2010cited by this paper
• Chemical cross-linking with NHS esters: a systematic study on amino acid reactivities.

  2009cited by this paper
• Comparative Photochemistry of Animal Type 1 and Type 4 Cryptochromes†

  2009cited by this paper
• I-TASSER server for protein 3D structure prediction

  2008cited by this paper
• Chemically induced and light-independent cryptochrome photoreceptor activation.

  2008cited by this paper
• Calcium-dependent conformational changes in guanylate cyclase-activating protein 2 monitored by cysteine accessibility.

  2007cited by this paper
• Targeting C-reactive protein for the treatment of cardiovascular disease

  2006cited by this paper
• In-gel digestion for mass spectrometric characterization of proteins and proteomes

  2006cited by this paper
• Scalable molecular dynamics with NAMD

  2005cited by this paper
• M-ZDOCK: a grid-based approach for Cn symmetric multimer docking

  2005cited by this paper
• N-Terminal Domain–Mediated Homodimerization Is Required for Photoreceptor Activity of Arabidopsis CRYPTOCHROME 1

  2005cited by this paper
• Discriminative topological features reveal biological network mechanisms

  2004cited by this paper
• Cryptochromes and neuronal-activity markers colocalize in the retina of migratory birds during magnetic orientation.

  2004cited by this paper
• Dimerization of Cell Surface Receptors in Signal Transduction Review

  2004cited by this paper
• Extending the treatment of backbone energetics in protein force fields: Limitations of gas‐phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations

  2004cited by this paper
• Retinal cryptochrome in a migratory passerine bird: a possible transducer for the avian magnetic compass

  2004cited by this paper
• Identification of a new cryptochrome class. Structure, function, and evolution.

  2003cited by this paper
• ZDOCK: An initial‐stage protein‐docking algorithm

  2003cited by this paper
• A novel shape complementarity scoring function for protein‐protein docking

  2003cited by this paper
• Structural basis of the redox switch in the OxyR transcription factor.

  2001cited by this paper
• Redox Switch of Hsp33 Has a Novel Zinc-binding Motif*

  2000cited by this paper
• A model for photoreceptor-based magnetoreception in birds.

  2000cited by this paper
• Cryptochromes: blue light receptors for plants and animals.

  1999cited by this paper
• Exact and efficient analytical calculation of the accessible surface areas and their gradients for macromolecules

  1998cited by this paper
• The Role of the Thioredoxin and Glutaredoxin Pathways in Reducing Protein Disulfide Bonds in the Escherichia coliCytoplasm*

  1997cited by this paper
• VMD: visual molecular dynamics.

  1996cited by this paper
• Dimerization of cell surface receptors in signal transduction.

  1995cited by this paper
• Putative blue-light photoreceptors from Arabidopsis thaliana and Sinapis alba with a high degree of sequence homology to DNA photolyase contain the two photolyase cofactors but lack DNA repair activity.

  1995cited by this paper
• Constant pressure molecular dynamics simulation: The Langevin piston method

  1995cited by this paper
• Comparison of simple potential functions for simulating liquid water

  1983cited by this paper
• A discussion of the solution for the best rotation to relate two sets of vectors

  1978cited by this paper

• Light-induced conformational switching and magnetic sensitivity of Drosophila cryptochrome

  2025cites this paper
• Spectroscopic Characterization of Radical Pair Photochemistry in Nonmigratory Avian Cryptochromes: Magnetic Field Effects in GgCry4a

  2025cites this paper
• A Charge-reversal Point Mutation Completely Depletes Flavin Chromophore from European Robin Cryptochrome 4a Protein

  2025cites this paper
• RadicalPy: A Tool for Spin Dynamics Simulations

  2024cites this paper
• The Effect of Spin Relaxation on Magnetic Compass Sensitivity in ErCry4a.

  2024cites this paper
• Cryptochrome magnetoreception: Time course of photoactivation from non-equilibrium coarse-grained molecular dynamics

  2024cites this paper
• Different receptor models show differences in ligand binding strength and location: a computational drug screening for the tick-borne encephalitis virus

  2024cites this paper
• Possibility of two-dimensional ordering of cryptochrome 4a from European robin.

  2024cites this paper