9K0F
Cryo-EM structure of Amyloid-beta42-4b polymorph 3
Summary for 9K0F
| Entry DOI | 10.2210/pdb9k0f/pdb |
| EMDB information | 61946 |
| Descriptor | Amyloid-beta A4 protein, Amyloid-beta protein 40 (3 entities in total) |
| Functional Keywords | helical fibril, amyloid-beta, protein fibril, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 12 |
| Total formula weight | 45414.19 |
| Authors | |
| Primary citation | Wei, Q.,Liu, D.,Xia, W.,Wang, F.,Huang, L.,Zhang, J.,Wang, X.,Xu, Z.,He, C.,Li, W.,Shi, X.,Wang, C.,Liu, Y.,Liu, C.,Dong, S. An O-glycopeptide participates in the formation of distinct A beta 42 fibril structures and attenuates A beta 42 neurotoxicity. Nat Commun, 16:5815-5815, 2025 Cited by PubMed Abstract: The self-assembly of biomolecules through noncovalent interactions is critical in both physiological and pathological processes, as exemplified by the assembly of amyloid β peptide (Aβ) into oligomers or fibrils in Alzheimer's disease (AD). Developing molecules that can modulate this assembly process holds significant mechanistic and therapeutic potential. In this study, we identified glycopeptides as a class of protein aggregation modulators, showing that β-N-acetylgalactosamine (β-GalNAc)-modified Aβ promotes Aβ fibrillation while reducing its toxic oligomers. Using biochemical assays, cryo-EM, and molecular dynamics simulations, we demonstrated that β-GalNAc-modified Aβ coassembles with Aβ, forming unique fibril structures stabilized by both hydrophobic interactions and an organized hydrogen bond network facilitated by the glycopeptide. Importantly, β-GalNAc-modified Aβ can alleviate the neurotoxicity of Aβ in neuronal cells and an AD male mouse model. These findings underscore the potential of glycopeptides in regulating amyloid aggregation and provide structural insights for designing molecules targeting amyloid-related pathologies. PubMed: 40593714DOI: 10.1038/s41467-025-60978-w PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.8 Å) |
Structure validation
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