Allosteric modulation of fluorescence revealed by hydrogen bond dynamics in a genetically encoded maltose biosensor
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Abstract
Genetically encoded fluorescent biosensors (GEFBs) proved to be reliable tracers for many metabolites and cellular processes. In the simplest case, a fluorescent protein (FP) is genetically fused to a sensing protein which undergoes a conformational change upon ligand binding. This drives a rearrangement in the chromophore environment and changes the spectral properties of the FP. Structural determinants of successful biosensors are revealed only in hindsight when the crystal structures of both ligand‐bound and ligand‐free forms are available. This makes the development of new biosensors for desired analytes a long trial‐and‐error process. In the current study, we conducted μs‐long all atom molecular dynamics (MD) simulations of a maltose biosensor in both the apo (dark) and holo (bright) forms. We performed detailed hydrogen bond occupancy analyses to shed light on the mechanism of ligand induced conformational change in the sensor protein and its allosteric effect on the chromophore environment. We find that two strong indicators for distinguishing bright and dark states of biosensors are due to substantial changes in hydrogen bond dynamics in the system and solvent accessibility of the chromophore.
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- Authors
- Berksoz, M., & Atilgan, C.
- Affiliations
- Faculty of Engineering and Natural Sciences, Sabanci University Turkey
- ORCID
- Atilgan, Canan
- Venue
- Proteins: Structure, Function, and Bioinformatics
- Publisher
- Wiley
- Published
- 2024-04-04
- Volume
- 92
- Issue
- 8
- Pages
- 923-932
- ISSN
- 0887-3585 (ISSN-L)
- 1097-0134
- OpenAlex
- W4393942395
- Cited by
- 8
- References
- 51
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Update notices
- correction (2024-12-20)
- Open access
- green
- dx.doi.org
- Locations
- Proteins Structure Function and Bioinformatics (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Sabanci University (submittedVersion)
- Funders
- Türkiye Bilimsel ve Teknolojik Araştırma Kurumu (121Z329)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › bioluminescence and chemiluminescence research
- Keywords
- genetically encoded fluorescent sensors, allosteric modulation, hydrogen bond dynamics, ligand-induced conformational change, apo and holo states, solvent accessibility, molecular dynamics simulation
- MeSH terms
- Allosteric Regulation, Fluorescence, Hydrogen Bonding, Ligands, Maltose, Protein Binding, Protein Conformation, Biosensing Techniques, Molecular Dynamics Simulation
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