Aβ42 assembles into specific β-barrel pore-forming oligomers in membrane-mimicking environments
Serra-Batiste, M; Ninot-Pedrosa, M; Bayoumi, M; Gairí, M; Maglia, G; Carulla, N
| HERO ID | 3860278 |
|---|---|
| In Press | No |
| Year | 2016 |
| Title | Aβ42 assembles into specific β-barrel pore-forming oligomers in membrane-mimicking environments |
| Authors | Serra-Batiste, M; Ninot-Pedrosa, M; Bayoumi, M; Gairí, M; Maglia, G; Carulla, N |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 113 |
| Issue | 39 |
| Page Numbers | 10866-10871 |
| Abstract | The formation of amyloid-β peptide (Aβ) oligomers at the cellular membrane is considered to be a crucial process underlying neurotoxicity in Alzheimer's disease (AD). Therefore, it is critical to characterize the oligomers that form within a membrane environment. To contribute to this characterization, we have applied strategies widely used to examine the structure of membrane proteins to study the two major Aβ variants, Aβ40 and Aβ42. Accordingly, various types of detergent micelles were extensively screened to identify one that preserved the properties of Aβ in lipid environments-namely the formation of oligomers that function as pores. Remarkably, under the optimized detergent micelle conditions, Aβ40 and Aβ42 showed different behavior. Aβ40 aggregated into amyloid fibrils, whereas Aβ42 assembled into oligomers that inserted into lipid bilayers as well-defined pores and adopted a specific structure with characteristics of a β-barrel arrangement that we named β-barrel pore-forming Aβ42 oligomers (βPFOsAβ42). Because Aβ42, relative to Aβ40, has a more prominent role in AD, the higher propensity of Aβ42 to form βPFOs constitutes an indication of their relevance in AD. Moreover, because βPFOsAβ42 adopt a specific structure, this property offers an unprecedented opportunity for testing a hypothesis regarding the involvement of βPFOs and, more generally, membrane-associated Aβ oligomers in AD. |
| Doi | 10.1073/pnas.1605104113 |
| Pmid | 27621459 |
| Wosid | WOS:000383954700039 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | Alzheimer's disease; amyloid-beta peptide; membrane pore; oligomer |