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

IF 3.5 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
ACS Chemical Biology Pub Date : 2025-03-21 Epub Date: 2025-02-21 DOI:10.1021/acschembio.4c00576
Marta Majewska, Maja Hanić, Rabea Bartölke, Jessica Schmidt, Justyna Bożek, Luca Gerhards, Henrik Mouritsen, Karl-Wilhelm Koch, Ilia A Solov'yov, Izabella Brand
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引用次数: 0

Abstract

Since the middle of the 20th century, long-distance avian migration has been known to rely partly on 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 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.

欧洲知更鸟隐色素-4a与脂质双分子层有序结合,满足磁接受的分子水平条件。
自20世纪中叶以来,人们已经知道长距离鸟类迁徙在一定程度上依赖于地磁场。然而,潜在的感觉机制仍未完全了解。隐色素-4a (ErCry4a),发现于欧洲知更鸟(Erithacus rubecula),夜游鸣禽,已被认为是一种磁感觉分子。它通过所谓的自由基对机制对外部磁场敏感。ErCry4a主要位于眼睛双锥光感受器细胞的外段,其中包含堆叠和高度有序的膜,可以促进ErCry4a的各向异性附着,从而实现磁罗盘感应。在这里,我们使用实验和计算方法研究了ErCry4a与模拟脊椎动物光感受器细胞外节脂质组成的模型膜可能的相互作用。实验结果表明,ErCry4a与膜的附着可以通过脂质双分子层外叶脂质分子的物理状态(每个脂质平均面积)来控制。此外,偏振调制红外反射吸收光谱使我们能够确定在膜相关状态下ErCry4a中α-螺旋的构象、运动自由度和平均取向。原子分子动力学研究支持了实验结果。与没有蛋白与膜结合的情况相比,ErCry4a膜结合导致相互作用能降低~ 1000 kcal mol-1。在分子水平上,这种结合似乎涉及到带负电荷的磷酸丝氨酸脂质羧酸基团和ErCry4a的c端残基。我们的研究揭示了ErCry4a与脂质膜的潜在直接相互作用,并讨论了这种结合如何成为ErCry4a进一步传播磁信号从而发挥磁受体作用的重要步骤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Chemical Biology
ACS Chemical Biology 生物-生化与分子生物学
CiteScore
7.50
自引率
5.00%
发文量
353
审稿时长
3.3 months
期刊介绍: ACS Chemical Biology provides an international forum for the rapid communication of research that broadly embraces the interface between chemistry and biology. The journal also serves as a forum to facilitate the communication between biologists and chemists that will translate into new research opportunities and discoveries. Results will be published in which molecular reasoning has been used to probe questions through in vitro investigations, cell biological methods, or organismic studies. We welcome mechanistic studies on proteins, nucleic acids, sugars, lipids, and nonbiological polymers. The journal serves a large scientific community, exploring cellular function from both chemical and biological perspectives. It is understood that submitted work is based upon original results and has not been published previously.
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