9QYL
Alpha-synuclein fibril type 1A polymorph in the presence of ATP
Summary for 9QYL
| Entry DOI | 10.2210/pdb9qyl/pdb |
| EMDB information | 53453 |
| Descriptor | Alpha-synuclein (1 entity in total) |
| Functional Keywords | alpha-synuclein, amyloid fibril, type 1a polymorph, protein aggregation, neurodegeneration, parkinson's disease, atp binding, atp hydrolysis, cryo-em structure, neuropeptide |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 24 |
| Total formula weight | 347426.59 |
| Authors | Frey, L.,Riek, R.,Wittung Stafshede, P. (deposition date: 2025-04-18, release date: 2025-10-29, Last modification date: 2025-12-10) |
| Primary citation | Frey, L.,Buratti, F.A.,Horvath, I.,Parate, S.,Kumar, R.,Riek, R.,Wittung-Stafshede, P. ATP Hydrolysis by alpha-Synuclein Amyloids is Mediated by Enclosing beta-Strand. Adv Sci, 12:e08441-e08441, 2025 Cited by PubMed Abstract: Pathological amyloids, like those formed by α-synuclein in Parkinson's disease, are recently found to catalyze the hydrolysis of model substrates in vitro. Here it is reported that the universal energy molecule ATP is another substrate for α-synuclein amyloid chemical catalysis. To reveal the underlying mechanism, the high-resolution cryo-EM structure of the amyloids in the presence of ATP is solved. The structure reveals a type 1A amyloid fold with an additional β-strand involving residues 16-22 that wraps around the ATP, creating an enclosed cavity at the interface of the protofilaments. Mutations of putative ATP-interacting residues in the cavity and the additional β-strand showed that replacing any one of Lys21, Lys23, Lys43, Lys45, and Lys60 with Ala reduced amyloid-mediated ATPase activity. High-resolution structural analysis of Lys21Ala α-synuclein amyloids in the presence of ATP reveals the same fold as wild-type α-synuclein amyloids but without the extra β-strand and with ATP oriented differently. It is concluded that positively-charged side chains, along with ordering of the N-terminal part into a β-strand, enclosing the cavity, are essential parameters governing ATP hydrolysis by α-synuclein amyloids. Amyloid-catalyzed ATP hydrolysis may hamper ATP-dependent rescue systems near amyloid deposits in vivo. PubMed: 41099718DOI: 10.1002/advs.202508441 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.08 Å) |
Structure validation
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