Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	A Novel α-Synuclein K58N Missense Variant in a Patient with Parkinson's Disease.
Journal, issue, pages	Mov Disord, Vol. 40, Issue 12, Page 2732-2745, Year 2025
Publish date	Sep 4, 2025
Authors	Mohammed Al-Azzani / Sandrina Weber / Nagendran Ramalingam / Maria Ramón / Liana Shvachiy / Gonçalo Mestre / Michael Zech / Kevin Sicking / Alain Ibáñez de Opakua / Vidyashree Jayanthi / Leslie Amaral / Aishwarya Agarwal / Aswathy Chandran / Susana R Chaves / Juliane Winkelmann / Claudia Trenkwalder / Maike Schwager / Silke Pauli / Ulf Dettmer / Claudio O Fernández / Janin Lautenschläger / Markus Zweckstetter / Ruben Fernandez-Busnadiego / Brit Mollenhauer / Tiago Fleming Outeiro /
PubMed Abstract	BACKGROUND: Parkinson's disease (PD) is a complex multifactorial disorder with a genetic component in about 15% of cases. Multiplications and point mutations in SNCA gene, encoding α-synuclein (aSyn) ...BACKGROUND: Parkinson's disease (PD) is a complex multifactorial disorder with a genetic component in about 15% of cases. Multiplications and point mutations in SNCA gene, encoding α-synuclein (aSyn), are linked to rare familial forms of PD. OBJECTIVE: Our goal was to assess the clinical presentation and the biological effects of a novel K58N aSyn mutation identified in a patient with PD. METHODS: We describe the clinical presentation associated with the novel mutation, together with genetic testing through whole exome sequencing (WES). Furthermore, we conducted extensive biophysical and cellular assays to assess the functional consequences of this novel variant. RESULTS: The patient exhibited typical features of sporadic PD with early onset and a benign disease course. WES showed a novel heterozygous missense variant in SNCA (NM_000345.4, c.174G>C; p.K58N). A positive family history of PD was evident, because both a parent and a grandparent had been diagnosed with PD but were deceased. The patient underwent deep brain stimulation surgery 13 years postdiagnosis, showing stable, long-term improvements in motor symptoms. Biophysical studies demonstrated K58N substitution causes local structural effects, disrupts membrane binding, and enhances aSyn in vitro aggregation. In cellular systems, K58N aSyn produces fewer inclusions per cell and does not form condensates. The variant increases aSyn cytoplasmic distribution and displays aberrant activity-dependent dynamic serine-129 phosphorylation. CONCLUSIONS: The clinical presentation associated with the novel K58N aSyn mutation suggests a relatively benign PD course consistent with the phenotypic spectrum of idiopathic PD. Overall, our molecular studies provide novel insight into the biology and pathobiology of aSyn. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
External links	Mov Disord / PubMed:40905240 / PubMed Central
Methods	EM (single particle)
Resolution	3.0 - 3.7 Å
Structure data	52166 9hgs EMDB-52166, PDB-9hgs: In vitro grown G14R Alpha-Synuclein Fibrils Method: EM (single particle) / Resolution: 3.0 Å 52458 9hxa EMDB-52458, PDB-9hxa: In vitro grown K58N Alpha-Synuclein Fibrils Method: EM (single particle) / Resolution: 3.7 Å
Source	homo sapiens (human)
Keywords	PROTEIN FIBRIL / Alpha-Synuclein / G14R Mutation / Fibrils / Cryo-EM / Protein Aggregation / Amyloid Structure / K58N Mutation