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Purification of Human S100A12 and Its Ion-induced Oligomers for Immune Cell Stimulation
Published on: September 29, 2019
Intrinsic disorder in S100 proteins.
Sergei E Permyakov1, Ramis G Ismailov, Bin Xue
1Institute for Biological Instrumentation of the Russian Academy of Sciences, Institutskaya str., 7, Pushchino, Moscow region 142290, Russia. permyakov.s@gmail.com
Molecular Biosystems
|April 30, 2011
Summary
S100 proteins, despite not being intrinsically disordered proteins (IDPs), exhibit significant disorder crucial for their broad functional diversity. This intrinsic disorder, particularly in specific regions, enables versatile target binding and protein interactions.
Area of Science:
- Biochemistry
- Structural Biology
- Protein Science
Background:
- S100 proteins are the largest subfamily of EF-hand proteins, known for their evolutionary youth and broad functional diversity.
- Their adaptability to various targets is a characteristic often seen in intrinsically disordered proteins (IDPs), yet S100 proteins are not typically classified as such.
Purpose of the Study:
- To investigate the extent and role of intrinsic disorder in S100 proteins.
- To understand how intrinsic disorder contributes to the functional diversity and target recognition of S100 proteins.
Main Methods:
- Bioinformatic prediction of intrinsic disorder using tools like PONDR® VSL2.
- Analysis of conserved disordered regions, post-translational modification (PTM) sites, and evolutionary hotspots.
- Comparison of disorder levels in dimerization sites versus target-binding sites.
Main Results:
- 62% of S100 proteins are predicted to have intrinsic disorder, with specific regions like the hinge and pseudo EF-hand loop being key disordered areas.
- Post-translational modifications destabilize S100 proteins, while metal-binding and dimerization promote stability.
- Disordered regions, particularly in the hinge and helix III, are critical for target recognition, accounting for 86% of S100 protein interactions.
Conclusions:
- Intrinsic disorder is a fundamental property of many S100 proteins, essential for their functional versatility.
- The structural flexibility of disordered regions directly facilitates the recognition of diverse protein targets.
- Understanding S100 protein disorder provides insights into their roles in various biological processes.
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