Article
Differential Interactome and Innate Immune Response Activation of Two Structurally Distinct Misfolded Protein Oligomers
Author/s | Mannini, Benedetta
Vecchi, Giulia Labrador Garrido, Adahir Fabre, Bertrand Pozo Pérez, David Dobson, Christopher M. Roodveldt, Cintia |
Department | Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología |
Publication Date | 2019 |
Deposit Date | 2024-01-19 |
Published in |
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Abstract | The formation of misfolded protein oligomers during early stages of amyloid aggregation and the activation of neuroinflammatory responses are two key events associated with neurodegenerative diseases. Although it has been ... The formation of misfolded protein oligomers during early stages of amyloid aggregation and the activation of neuroinflammatory responses are two key events associated with neurodegenerative diseases. Although it has been established that misfolded oligomers are involved in the neuroinflammatory process, the links between their structural features and their functional effects on the immune response remain unknown. To explore such links, we took advantage of two structurally distinct soluble oligomers (type A and B) of protein HypF-N and compared the elicited microglial inflammatory responses. By using confocal microscopy, protein pull-down, and high-throughput mass spectrometry, we found that, even though both types bound to a common pool of microglial proteins, type B oligomers—with a lower solvent-exposed hydrophobicity—showed enhanced protein binding, correlating with the observed inflammatory response. Furthermore, the interactome associated with inflammatory-mediated neurodegeneration revealed previously unidentified receptors and signaling molecules likely to be involved in the oligomer-elicited innate immune response. |
Funding agencies | Cambridge Centre for Misfolding Diseases EMBO FEBS (Short-Term Fellowship) Italian Society of Biochemistry and Molecular Biology Programa "Atraccion de Talento", University of Seville Programa "Ramon y Cajal", Spanish Ministry of Economy Regional Ministry of Economy Spanish Ministry of Economy |
Project ID. | ASTF 450-2013
RYC-2017-23127 P11-CTS-8161 PAIDI2020 CTS-677 RTC-2015-3309-1 ISCIII CPII16/58 PI14-1600 RTI2018-098432-B-I00 |
Citation | Mannini, B., Vecchi, G., Labrador Garrido, A., Fabre, B., Pozo Pérez, D., Dobson, C.M., Roodveldt, C. y Roodveldt, C. (2019). Differential Interactome and Innate Immune Response Activation of Two Structurally Distinct Misfolded Protein Oligomers. ACS Chemical Neuroscience, 18 (8), 3464-3478. https://doi.org/0.1021/acschemneuro.9b00088.. |
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