Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers
Somatostatin (SST14) is strongly related to Alzheimer's disease (AD), as its levels decline during aging, it regulates the proteolytic degradation of the amyloid beta peptide (Aβ), and it binds to Aβ oligomers in vivo. Recently, the 3D structure of a membrane-associated β-sheet pore-forming tetramer...
| Authors: | ; ; ; |
|---|---|
| Format: | Article |
| Status: | Accepted version |
| Publication date: | 2020 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/172183 |
| Online Access: | https://hdl.handle.net/2445/172183 |
| Access Level: | Open access |
| Keyword: | Malaltia d'Alzheimer Oligòmers Alzheimer's disease Oligomers |
| _version_ | 1878733022571790337 |
|---|---|
| author | Puig Gomà-Camps, Eduard |
| author2 | Tolchard, James Riera i Escalé, Antoni Carulla Casanovas, Natàlia |
| author2_role | author author author |
| author_browse | Carulla Casanovas, Natàlia Puig Gomà-Camps, Eduard Riera i Escalé, Antoni Tolchard, James |
| author_facet | Puig Gomà-Camps, Eduard Tolchard, James Riera i Escalé, Antoni Carulla Casanovas, Natàlia |
| author_role | author |
| collection | Dipòsit Digital de la UB |
| description | Somatostatin (SST14) is strongly related to Alzheimer's disease (AD), as its levels decline during aging, it regulates the proteolytic degradation of the amyloid beta peptide (Aβ), and it binds to Aβ oligomers in vivo. Recently, the 3D structure of a membrane-associated β-sheet pore-forming tetramer (βPFOAβ(1−42) tetramer) has been reported. Here, we show that SST14 binds selectively to the βPFOAβ(1−42) tetramer with a KD value of ∼40 μM without binding to monomeric Aβ(1−42). Specific NMR chemical shift perturbations, observed during titration of SST14, define a binding site in the βPFOAβ(1−42) tetramer and are in agreement with a 2:1 stoichiometry determined by both native mass spectroscopy and isothermal titration calorimetry. These results enabled us to perform driven docking and model the binding mode for the interaction. The present study provides additional evidence on the relation between SST14 and the amyloid cascade and positions the βPFOAβ(1−42) tetramer as a relevant aggregation form of Aβ and as a potential target for AD. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_4e895ea9d3ca4d445c2cbc33511bdd55 |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/172183 |
| publishDate | 2020 |
| publishDateSort | 2020 |
| publisher | American Chemical Society |
| publisherStr | American Chemical Society |
| reponame_str | Dipòsit Digital de la UB |
| spelling | Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers Puig Gomà-Camps, Eduard Tolchard, James Riera i Escalé, Antoni Carulla Casanovas, Natàlia Malaltia d'Alzheimer Oligòmers Alzheimer's disease Oligomers Somatostatin (SST14) is strongly related to Alzheimer's disease (AD), as its levels decline during aging, it regulates the proteolytic degradation of the amyloid beta peptide (Aβ), and it binds to Aβ oligomers in vivo. Recently, the 3D structure of a membrane-associated β-sheet pore-forming tetramer (βPFOAβ(1−42) tetramer) has been reported. Here, we show that SST14 binds selectively to the βPFOAβ(1−42) tetramer with a KD value of ∼40 μM without binding to monomeric Aβ(1−42). Specific NMR chemical shift perturbations, observed during titration of SST14, define a binding site in the βPFOAβ(1−42) tetramer and are in agreement with a 2:1 stoichiometry determined by both native mass spectroscopy and isothermal titration calorimetry. These results enabled us to perform driven docking and model the binding mode for the interaction. The present study provides additional evidence on the relation between SST14 and the amyloid cascade and positions the βPFOAβ(1−42) tetramer as a relevant aggregation form of Aβ and as a potential target for AD. American Chemical Society https://hdl.handle.net/2445/172183 |
| spellingShingle | Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers Puig Gomà-Camps, Eduard Malaltia d'Alzheimer Oligòmers Alzheimer's disease Oligomers |
| status_str | acceptedVersion |
| title | Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers |
| title_full | Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers |
| title_fullStr | Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers |
| title_full_unstemmed | Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers |
| title_short | Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers |
| title_sort | Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers |
| topic | Malaltia d'Alzheimer Oligòmers Alzheimer's disease Oligomers |
| topic_facet | Malaltia d'Alzheimer Oligòmers Alzheimer's disease Oligomers |
| url | https://hdl.handle.net/2445/172183 |