Genetically encoded crosslinkers to address protein-protein interactions.
1Faculty of Life Science, Institute of Biochemistry, Leipzig University, Leipzig, Germany.
Protein Science : a Publication of the Protein Society
|April 7, 2023
Summary
Genetically encoded noncanonical amino acids (ncAAs) enable photo- and chemical crosslinking to study protein interactions in cells. Recent advancements expand their use in structural biology and drug development.
Area of Science:
- Biochemistry
- Molecular Biology
- Chemical Biology
Background:
- Noncanonical amino acids (ncAAs) are powerful tools for studying protein interactions.
- Genetically encoded crosslinking ncAAs have matured beyond initial proof-of-concept studies.
- These tools are increasingly integrated into modern biological research approaches.
Purpose of the Study:
- To provide an overview of available photo-activatable and electrophilic ncAAs for crosslinking.
- To highlight recent advancements, including ncAAs for SuFEx click chemistry and photo-activatable chemical crosslinking.
- To showcase applications of genetically encoded crosslinkers in live-cell studies and structural biology.
Main Methods:
- Review of existing literature on photo- and chemical crosslinking ncAAs.
- Focus on recent developments in ncAAs for SuFEx click chemistry and photo-activatable chemical crosslinking.
- Presentation of case studies demonstrating the application of genetically encoded crosslinkers.
Main Results:
- Overview of diverse photo- and electrophilic ncAAs for crosslinking applications.
- Demonstration of ncAAs' utility in capturing protein-protein interactions in live cells.
- Examples of stabilizing protein complexes for structural studies and deriving in-cell structural information.
Conclusions:
- Genetically encoded crosslinking ncAAs are versatile tools for biological research.
- Recent ncAAs facilitate advanced applications, including structural biology and drug discovery.
- Future applications include the development of covalent drugs using GECX-ncAAs.
Keywords:
affinity crosslinkinggenetic code expansiongenetically encoded chemical crosslinkerslive-cell crosslinkingphoto-crosslinkingprotein-protein interactionsunnatural amino acidsMore Related Videos
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