9HGS
In vitro grown G14R Alpha-Synuclein Fibrils
Summary for 9HGS
| Entry DOI | 10.2210/pdb9hgs/pdb |
| EMDB information | 52166 |
| Descriptor | Alpha-synuclein (1 entity in total) |
| Functional Keywords | alpha-synuclein, g14r mutation, fibrils, cryo-em, protein aggregation, amyloid structure, protein fibril |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 14576.25 |
| Authors | Sicking, K.,Fernandez-Busnadiego, R. (deposition date: 2024-11-20, release date: 2025-01-29, Last modification date: 2025-03-12) |
| Primary citation | Al-Azzani, M.,Weber, S.,Ramalingam, N.,Ramon, M.,Shvachiy, L.,Mestre, G.,Zech, M.,Sicking, K.,Ibanez de Opakua, A.,Jayanthi, V.,Amaral, L.,Agarwal, A.,Chandran, A.,Chaves, S.R.,Winkelmann, J.,Trenkwalder, C.,Schwager, M.,Pauli, S.,Dettmer, U.,Fernandez, C.O.,Lautenschlager, J.,Zweckstetter, M.,Busnadiego, R.F.,Mollenhauer, B.,Outeiro, T.F. A novel alpha-synuclein K58N missense variant in a patient with Parkinson's disease. Medrxiv, 2025 Cited by PubMed Abstract: Mutations and multiplications in the SNCA , encoding alpha-synuclein (aSyn), are associated with familial forms of Parkinson's disease (PD). We report the identification of a novel missense mutation (NM_000345.4, cDNA 174G>C; protein K58N) in a PD patient using whole exome sequencing, and describe comprehensive molecular and cellular analysss of the effects of this novel mutation. The patient exhibited typical sporadic PD with early onset and a benign disease course. Biophysical studies revealed that the K58N substitution causes local structural effects, disrupts binding to membranes, and enhances aSyn in vitro aggregation. K58N aSyn produces fewer inclusions per cell, and fails to undergo condensate formation. The mutation increases the cytoplasmic distribution of the protein, and has minimal effect on the dynamic reversibility of serine-129 phosphorylation. In total, the identification of this novel mutation advances our understanding of aSyn biology and pathobiology. PubMed: 39990587DOI: 10.1101/2025.02.07.25321793 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3 Å) |
Structure validation
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