Moysa, A, Steczkiewicz, K, Niedzialek, D et al. (4 more authors) (2021) A model of full-length RAGE in complex with S100B. Structure, 29 (9). pp. 989-1002. ISSN 0969-2126
Abstract
The receptor for advanced glycation end products (RAGE) is an immunoglobulin-type multiligand transmembrane protein expressed in numerous cell types, including the central nervous system cells. RAGE interaction with S100B, released during brain tissue damage, leads to RAGE upregulation and initialization of a spiral proinflammatory associated with different neural disorders. Here, we present the structural characterization of the hetero-oligomeric complex of the full-length RAGE with S100B, obtained by a combination of mass spectrometry-based methods and molecular modeling. We predict that RAGE functions as a tightly packed tetramer exposing a positively charged surface formed by V domains for S100B binding. Based on HDX results we demonstrate an allosteric coupling of the distal extracellular V domains and the transmembrane region, indicating a possible mechanism of signal transmission by RAGE across the membrane. Our model provides an insight into RAGE-ligand interactions, providing a basis for the rational design of the therapeutic modifiers of its activity.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 Elsevier Ltd. This is an author produced version of an article published in Structure. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | HDX-MS; membrane proteins; molecular modeling; native MS; RAGE; receptor for advanced glycation end products; structural proteomics; XL-MS |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 05 Jul 2021 12:59 |
Last Modified: | 04 Jul 2022 12:43 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.str.2021.04.002 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:175759 |
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