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Detection of Heterodimerization of Protein Isoforms Using an in Situ Proximity Ligation Assay
Published on: October 20, 2018
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A subset of calcium-binding S100 proteins show preferential heterodimerization
Donald E Spratt1, Kathryn R Barber1, Nicole M Marlatt1
1Department of Biochemistry, The University of Western Ontario, London, Canada.
The FEBS Journal
|February 6, 2019
Summary
Protein oligomerization is crucial for function and disease. This study reveals that S100 heterodimers, like S100A1:S100B, are more common than homodimers, impacting cellular roles.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Protein oligomerization is essential for cellular functions including transcription, muscle contraction, and protease activity.
- Dysregulated oligomerization is implicated in diseases like Alzheimer's.
- The S100 protein family, known for its dimeric nature, plays roles in enzyme regulation, cell repair, and growth.
Purpose of the Study:
- To develop and apply co-expression methods for identifying and quantifying homo- and heterodimers of S100 proteins.
- To investigate the formation of S100 heterodimers in calcium-free states.
- To explore the potential functional implications of S100 heterodimerization.
Main Methods:
- Utilized split Green Fluorescent Protein (GFP) trap methodology with various GFP variants.
- Employed co-expression systems for in vitro and in vivo analyses.
- Integrated Nuclear Magnetic Resonance (NMR) and mass spectrometry for validation.
Main Results:
- Demonstrated the predominant formation of specific S100 heterodimers over homodimers.
- Identified S100A1:S100B, S100A1:S100P, and S100A11:S100B as prevalent heterodimeric species.
- Quantified the distribution of homo- and heterodimers in calcium-free conditions.
Conclusions:
- Established novel tools for analyzing S100 protein homo- and heterodimerization.
- Heterodimerization is a significant factor in S100 protein interactions.
- Further research into S100 heterodimers may elucidate their specific roles and alter cellular functions.
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