Dynamic association of flavin cofactors to regulate flavoprotein function

Schnerwitzki, Danny; Vabulas, R. Martin

doi:10.1002/iub.2591

Cited by 2 publications

(2 citation statements)

References 47 publications

(109 reference statements)

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“…Dynamic, rather than static, association with FAD is being recognized as a common phenomenon in flavoproteins ( Schnerwitzki and Vabulas, 2022 ). It follows that, although the affinity for FAD is much weaker in Type II than in Type I/IV CRYs, specific cellular conditions (e.g., redox conditions, high compartmental FAD concentrations or the presence of binding partners) could augment FAD binding to Type II CRYs.…”

Section: Scenarios For Mammalian Cryptochrome Magnetoreceptionmentioning

confidence: 99%

Cryptochromes in mammals: a magnetoreception misconception?

Zhang,

Malkemper

2023

Front. Physiol.

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Cryptochromes are flavoproteins related to photolyases that are widespread throughout the plant and animal kingdom. They govern blue light-dependent growth in plants, control circadian rhythms in a light-dependent manner in invertebrates, and play a central part in the circadian clock in vertebrates. In addition, cryptochromes might function as receptors that allow animals to sense the Earth’s magnetic field. As cryptochromes are also present in mammals including humans, the possibility of a magnetosensitive protein is exciting. Here we attempt to provide a concise overview of cryptochromes in mammals. We briefly review their canonical role in the circadian rhythm from the molecular level to physiology, behaviour and diseases. We then discuss their disputed light sensitivity and proposed role in the magnetic sense in mammals, providing three mechanistic hypotheses. Specifically, mammalian cryptochromes could form light-induced radical pairs in particular cellular milieus, act as magnetoreceptors in darkness, or as secondary players in a magnetoreception signalling cascade. Future research can test these hypotheses to investigate if the role of mammalian cryptochromes extends beyond the circadian clock.

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Section: Scenarios For Mammalian Cryptochrome Magnetoreceptionmentioning

confidence: 99%

Cryptochromes in mammals: a magnetoreception misconception?

Zhang,

Malkemper

2023

Front. Physiol.

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“…Furthermore, the extent of cofactor-enzyme association may change depending on the cellular status or interaction partners present in flavoprotein complexes ( Hashida et al, 2004 ; Yazdanpanah et al, 2009 ). More research is needed to understand the dynamics of flavin associations ( Schnerwitzki and Vabulas, 2022 ).…”

Section: Mammalian Cryptochromes Associate With Fad Very Weaklymentioning

confidence: 99%

The structural and functional roles of the flavin cofactor FAD in mammalian cryptochromes

Calloni¹,

Vabulas

2023

Front. Mol. Biosci.

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The importance of circadian rhythms in human health and disease calls for a thorough understanding of the underlying molecular machinery, including its key components, the flavin adenine dinucleotide (FAD)-containing flavoproteins cryptochrome 1 and 2. Contrary to their Drosophila counterparts, mammalian cryptochromes are direct suppressors of circadian transcription and act independently of light. Light-independence poses the question regarding the role of the cofactor FAD in mammalian cryptochromes. The weak binding of the cofactor in vitro argues against its relevance and might be a functionless evolutionary remnant. From the other side, the FAD-binding pocket constitutes the part of mammalian cryptochromes directly related to their ubiquitylation by the ubiquitin ligase Fbxl3 and is the target for protein-stabilizing small molecules. Increased supplies of FAD stabilize cryptochromes in cell culture, and the depletion of the FAD precursor riboflavin with simultaneous knock-down of riboflavin kinase affects the expression of circadian genes in mice. This review presents the classical and more recent studies in the field, which help to comprehend the role of FAD for the stability and function of mammalian cryptochromes.

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Dynamic association of flavin cofactors to regulate flavoprotein function

Cited by 2 publications

References 47 publications

Cryptochromes in mammals: a magnetoreception misconception?

Cryptochromes in mammals: a magnetoreception misconception?

The structural and functional roles of the flavin cofactor FAD in mammalian cryptochromes

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