{"title":"Potential Activation Mechanism of Calcium Indicator WHaloCaMP1a Revealed by the Crystal Structure and Molecular Dynamics Simulations.","authors":"Kecheng Zhang, Nanhao Chen, Junwei Zhang, Zhixing Chen","doi":"10.1021/acs.biochem.5c00352","DOIUrl":null,"url":null,"abstract":"<p><p>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<sub>HTL</sub>. 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.</p>","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemistry Biochemistry","FirstCategoryId":"1","ListUrlMain":"https://doi.org/10.1021/acs.biochem.5c00352","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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 BD566HTL. 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.
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.
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