近日，法国格勒诺布尔阿尔卑斯大学教授Giorgio Schirò团队的研究认为综合结构动力学揭示了新的B12光感受器激活模式。相关论文于2026年2月4日发表在《自然》杂志上。

在这里，研究人员结合时间分辨和温度分辨的结构和光谱方法以及量子化学计算，从纳秒到秒详细描述了原型B12光感受器CarH4,5的光激活。基于初始四聚体暗态和最终单体光激活态的晶体结构5，他们对截断的B12结合域关键中间体的结构快照阐明了B12发色团腺苷钴胺素内钴碳键的光裂解如何引发一系列在整个CarH中传播的结构变化。可光性Co- c5 ‘键的断裂导致形成一种先前未知的加合物，该加合物将腺苷基的C4 ’位置连接到Co离子上，随后可以在更长的时间尺度上进行热裂解，从而释放腺苷基，最终导致四聚体解离。这种加合物将CarH与热激活的B12酶区分开来，它引导光激活途径，并作为光化学和光生物时间尺度之间的分子桥梁。他们研究的生物学相关性得到了DNA存在下全长CarH的动力学数据的证实。他们的结果提供了对CarH光激活的时空理解，并为设计用于光遗传学应用的B12依赖性光受体铺平了道路。

据了解，光感受器蛋白调节基本的生物过程，如视觉、光合作用和昼夜节律。一个大的光感受器亚家族将维生素B12衍生物用于光感应，与这些有机金属衍生物在热激活酶反应中的既定作用模式形成对比。B12光接受的确切分子机制及其与热途径的区别尚不清楚。

附：英文原文

Title: Integrated structural dynamics uncover a new B12 photoreceptor activation mode

Author: Rios-Santacruz, Ronald, Poddar, Harshwardhan, Pounot, Kevin, Heyes, Derren J., Coquelle, Nicolas, Mackintosh, Megan J., Johannissen, Linus O., Schianchi, Sara, Jeffreys, Laura N., De Zitter, Elke, Munro, Rory, Appleby, Martin, Axford, Danny, Beale, Emma V., Cliff, Matthew J., Dvila-Miliani, Mara C., Engilberge, Sylvain, Gotthard, Guillaume, Hadjidemetriou, Kyprianos, Hardman, Samantha J. O., Horrell, Sam, Hub, Jochen S., Ishihara, Kotone, Jaho, Sofia, Karras, Gabriel, Kataoka, Machika, Kawakami, Ryohei, Mason, Thomas, Okumura, Hideo, Owada, Shigeki, Owen, Robin L., Royant, Antoine, Saaret, Annica, Sakuma, Michiyo, Shanmugam, Muralidharan, Sugimoto, Hiroshi, Tono, Kensuke, Zala, Ninon, Beale, John H., Tosha, Takehiko, Colletier, Jacques-Philippe, Levantino, Matteo, Hay, Sam, Kozlowski, Pawel M., Leys, David, Scrutton, Nigel S., Weik, Martin, Schir, Giorgio

Issue&Volume: 2026-02-04

Abstract: Photoreceptor proteins regulate fundamental biological processes such as vision, photosynthesis and circadian rhythms1. A large photoreceptor subfamily uses vitamin B12 derivatives for light sensing2, contrasting with the well-established mode of action of these organometallic derivatives in thermally activated enzymatic reactions3. The exact molecular mechanism of B12 photoreception and how this differs from the thermal pathways remains unknown. Here we provide a detailed description of photoactivation in the prototypical B12 photoreceptor CarH4,5 from nanoseconds to seconds, combining time-resolved and temperature-resolved structural and spectroscopic methods with quantum chemical calculations. Building on the crystal structures of the initial tetrameric dark and final monomeric light-activated states5, our structural snapshots of key intermediates in the truncated B12-binding domain illustrate how photocleavage of a cobalt–carbon (Co–C) bond within the B12 chromophore adenosylcobalamin triggers a series of structural changes that propagate throughout CarH. Breakage of the photolabile Co–C5′ bond leads to the formation of a previously unknown adduct that links the C4′ position of the adenosyl moiety to the Co ion and can subsequently be cleaved thermally over longer timescales to allow release of the adenosyl group, ultimately causing tetramer dissociation4,5. This adduct, which differentiates CarH from thermally activated B12 enzymes, steers the photoactivation pathway and acts as the molecular bridge between photochemical and photobiological timescales. The biological relevance of our study is corroborated by kinetic data on full-length CarH in the presence of DNA. Our results offer a spatiotemporal understanding of CarH photoactivation and pave the way for designing B12-dependent photoreceptors for optogenetic applications.

DOI: 10.1038/s41586-025-10074-2

Source: https://www.nature.com/articles/s41586-025-10074-2