A model of full-length RAGE in complex with S100B.
Alexander Moysa1, Kamil Steczkiewicz1, Dorota Niedzialek1
1Institute of Biochemistry and Biophysics, PAS, Pawinskiego 5a, 02-109 Warsaw, Poland.
Structure (London, England : 1993)
|April 22, 2021
Summary
The receptor for advanced glycation end products (RAGE) forms a tetramer that binds S100B, a protein released during brain injury. This interaction reveals how RAGE signals across the cell membrane, offering targets for treating neural disorders.
Area of Science:
- Neuroscience
- Structural Biology
- Molecular Medicine
Background:
- The receptor for advanced glycation end products (RAGE) is a transmembrane protein crucial in the central nervous system.
- RAGE activation by S100B, released upon brain damage, triggers inflammation linked to neural disorders.
Purpose of the Study:
- To structurally characterize the complex formed between full-length RAGE and S100B.
- To elucidate the mechanism of RAGE-mediated signal transmission across the cell membrane.
Main Methods:
- Mass spectrometry-based techniques for structural determination.
- Molecular modeling to predict complex formation.
- Hydrogen-deuterium exchange (HDX) to study allosteric coupling.
Main Results:
- RAGE forms a tightly packed tetrameric complex with S100B.
- The V domains of RAGE present a positively charged surface for S100B binding.
- HDX data confirmed allosteric coupling between extracellular domains and the transmembrane region of RAGE.
Conclusions:
- The structural model provides insights into RAGE-S100B interactions.
- Identified RAGE oligomerization and allosteric signaling mechanisms.
- Offers a basis for designing therapeutic agents targeting RAGE activity in neural disorders.
