6RHY
Structure of pore-forming amyloid-beta tetramers
Summary for 6RHY
| Entry DOI | 10.2210/pdb6rhy/pdb |
| NMR Information | BMRB: 34396 |
| Descriptor | Amyloid beta A4 protein (1 entity in total) |
| Functional Keywords | amyloid, alzheimer's disease, membrane pore, oligomer, protein fibril |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 4 |
| Total formula weight | 18080.35 |
| Authors | Bardiaux, B.,Ciudad, S.,Carulla, N. (deposition date: 2019-04-23, release date: 2019-09-25, Last modification date: 2024-06-19) |
| Primary citation | Ciudad, S.,Puig, E.,Botzanowski, T.,Meigooni, M.,Arango, A.S.,Do, J.,Mayzel, M.,Bayoumi, M.,Chaignepain, S.,Maglia, G.,Cianferani, S.,Orekhov, V.,Tajkhorshid, E.,Bardiaux, B.,Carulla, N. A beta (1-42) tetramer and octamer structures reveal edge conductivity pores as a mechanism for membrane damage. Nat Commun, 11:3014-3014, 2020 Cited by PubMed Abstract: Formation of amyloid-beta (Aβ) oligomer pores in the membrane of neurons has been proposed to explain neurotoxicity in Alzheimer's disease (AD). Here, we present the three-dimensional structure of an Aβ oligomer formed in a membrane mimicking environment, namely an Aβ(1-42) tetramer, which comprises a six stranded β-sheet core. The two faces of the β-sheet core are hydrophobic and surrounded by the membrane-mimicking environment while the edges are hydrophilic and solvent-exposed. By increasing the concentration of Aβ(1-42) in the sample, Aβ(1-42) octamers are also formed, made by two Aβ(1-42) tetramers facing each other forming a β-sandwich structure. Notably, Aβ(1-42) tetramers and octamers inserted into lipid bilayers as well-defined pores. To establish oligomer structure-membrane activity relationships, molecular dynamics simulations were carried out. These studies revealed a mechanism of membrane disruption in which water permeation occurred through lipid-stabilized pores mediated by the hydrophilic residues located on the core β-sheets edges of the oligomers. PubMed: 32541820DOI: 10.1038/s41467-020-16566-1 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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