レンセラー大学の研究者が概日リズムに新たな光を当てる(Rensselaer Researcher Sheds New Light on Circadian Rhythms)

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2024-06-04 レンセラー工科大学 (RPI)

概日時計は、植物、菌類、昆虫、人間を含む多くの生物の重要なシステムと結びついており、これが乱れると特定の癌や自己免疫疾患のリスクが高まります。レンセラー工科大学のジェニファー・ハーリー博士の研究チームは、Neurospora crassaという菌類のFRQタンパク質がFRHタンパク質と複雑に相互作用することを発見しました。この相互作用は、概日時計を毎日光でリセットする必要がある砂時計型から、連続的なリズムを維持する持続振動子に変えます。この発見により、概日時計を操作してバイオ燃料生産や時差ぼけの対策、シフト労働者の健康管理などに応用する可能性が広がります。また、治療の最適なタイミングを見極める「クロノセラピー」も期待されています。

<関連情報>

時計タンパク質の相互作用と電荷ブロックの乱れが、砂時計を持続的な概日振動子に変える Disordered clock protein interactions and charge blocks turn an hourglass into a persistent circadian oscillator

Meaghan S. Jankowski,Daniel Griffith,Divya G. Shastry,Jacqueline F. Pelham,Garrett M. Ginell,Joshua Thomas,Pankaj Karande,Alex S. Holehouse & Jennifer M. Hurley
Nature Communications  Published:25 April 2024
DOI:https://doi.org/10.1038/s41467-024-47761-z

レンセラー大学の研究者が概日リズムに新たな光を当てる(Rensselaer Researcher Sheds New Light on Circadian Rhythms)

Abstract

Organismal physiology is widely regulated by the molecular circadian clock, a feedback loop composed of protein complexes whose members are enriched in intrinsically disordered regions. These regions can mediate protein-protein interactions via SLiMs, but the contribution of these disordered regions to clock protein interactions had not been elucidated. To determine the functionality of these disordered regions, we applied a synthetic peptide microarray approach to the disordered clock protein FRQ in Neurospora crassa. We identified residues required for FRQ’s interaction with its partner protein FRH, the mutation of which demonstrated FRH is necessary for persistent clock oscillations but not repression of transcriptional activity. Additionally, the microarray demonstrated an enrichment of FRH binding to FRQ peptides with a net positive charge. We found that positively charged residues occurred in significant “blocks” within the amino acid sequence of FRQ and that ablation of one of these blocks affected both core clock timing and physiological clock output. Finally, we found positive charge clusters were a commonly shared molecular feature in repressive circadian clock proteins. Overall, our study suggests a mechanistic purpose for positive charge blocks and yielded insights into repressive arm protein roles in clock function.

有機化学・薬学
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