钙指示剂WHaloCaMP1a晶体结构和分子动力学模拟揭示的电位活化机制

IF 3 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry Biochemistry Pub Date : 2025-09-26 DOI:10.1021/acs.biochem.5c00352

Kecheng Zhang, Nanhao Chen, Junwei Zhang, Zhixing Chen

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引用次数: 0

摘要

化学遗传指示器结合先进的有机荧光团，由于其结合了蛋白质的生物相容性和染料优越的光学性能，在生物传感器的开发中越来越受到欢迎。然而，尽管基于这些系统的各种生物传感器的发展，潜在的激活机制仍然不清楚。在这里，我们报道了最近开发的钙指示剂WHaloCaMP1a与罗丹明基荧光团BD566HTL配合物的第一个晶体结构。结合结构分析和分子动力学模拟，我们确定了WHaloCaMP1a的潜在激活机制，并揭示了传感器与BD566之间的新相互作用。这些发现为生物传感器的合理设计和蛋白质-染料协同进化的研究提供了新的见解。

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Potential Activation Mechanism of Calcium Indicator WHaloCaMP1a Revealed by the Crystal Structure and Molecular Dynamics Simulations.

Chemigenetic indicators combined with advanced organic fluorophores have become increasingly popular in biosensor development due to their integration of protein biocompatibility and the superior optical properties of dyes. However, despite the development of various biosensors based on these systems, the underlying activation mechanisms remain obscure. Here, we report the first crystal structure of the recently developed calcium indicator WHaloCaMP1a in complex with the rhodamine-based fluorophore BD566_HTL. Integrating structural analysis with molecular dynamics simulations, we identify a potential activation mechanism of WHaloCaMP1a and reveal novel interactions between the sensor and BD566. These findings provide new insights for the rational design of biosensors and the study of protein-dye coevolution.

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来源期刊

Biochemistry Biochemistry 生物-生化与分子生物学

CiteScore

5.50

自引率

3.40%

发文量

336

审稿时长

1-2 weeks

期刊介绍： Biochemistry provides an international forum for publishing exceptional, rigorous, high-impact research across all of biological chemistry. This broad scope includes studies on the chemical, physical, mechanistic, and/or structural basis of biological or cell function, and encompasses the fields of chemical biology, synthetic biology, disease biology, cell biology, nucleic acid biology, neuroscience, structural biology, and biophysics. In addition to traditional Research Articles, Biochemistry also publishes Communications, Viewpoints, and Perspectives, as well as From the Bench articles that report new methods of particular interest to the biological chemistry community.