Abstract
Targeting the receptor for the advanced glycation endproducts (RAGE) signalling has a potential for the prevention and treatment of several pathologies. Extracellular activation of RAGE triggers the interactions of the RAGE cytoplasmic tail with intracellular protein partners. Here the cytoplasmic tail of RAGE has been investigated by NMR as part of the full-length protein, in the presence of a membrane-mimicking environment. The isolated cytoplasmic tail has also been studied for comparison. The NMR spectra of the whole receptor show that some but not all residues belonging to the C-terminal region of the cytoplasmic tail have a large flexibility, while the membrane proximal region seems to be rigidly connected to the trans-membrane domain and ectodomains. The analysis indicates that the behavior of the cytoplasmic tail is strongly affected by its being part of the whole receptor. These results provide new insight towards the understanding of signal transduction by RAGE.
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Acknowledgments
This work has been supported by MIUR-FIRB contracts RBLA032ZM7, RBRN07BMCT and RBIP06LSS2, by Ente Cassa di Risparmio di Firenze, and by the European Commission, contracts Bio-NMR n. 261863, East-NMR n. 228461, STREP–SFMET n. 201640, SPINE2-COMPLEXES 031220, and We-NMR 261572.
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Borsi, V., Cerofolini, L., Fragai, M. et al. NMR characterization of the C-terminal tail of full-length RAGE in a membrane mimicking environment. J Biomol NMR 54, 285–290 (2012). https://doi.org/10.1007/s10858-012-9671-0
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DOI: https://doi.org/10.1007/s10858-012-9671-0