ArticleBiochemistry2011
Impact of autosomal recessive juvenile Parkinson's disease mutations on the structure and interactions of the parkin ubiquitin-like domain.
Article in Biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Parkinson's Disease in Saudi Patients: A Genetic Study.PloS one · 2015Trial
- Activation of parkin by a molecular glue.Nature communications · 2024Article
- Naturally occurring hyperactive variants of human parkin.Communications biology · 2024Article
- Structure-based design and characterization of Parkin-activating mutations.Life science alliance · 2023Article
- Mutational Impact on "in-Between-Ring" (IBR) Domain of PARKIN on Protein Stability and Function.Applied biochemistry and biotechnology · 2021Article
- PINK1/PARKIN signalling in neurodegeneration and neuroinflammation.Acta neuropathologica communications · 2020Review
- The landscape of Parkin variants reveals pathogenic mechanisms and therapeutic targets in Parkinson's disease.Human molecular genetics · 2019Article
- Impact of altered phosphorylation on loss of function of juvenile Parkinsonism-associated genetic variants of the E3 ligase parkin.The Journal of biological chemistry · 2018Article
- Specificity and disease in the ubiquitin system.Biochemical Society transactions · 2016Review
- Disruption of the autoinhibited state primes the E3 ligase parkin for activation and catalysis.The EMBO journal · 2015Article
- Structural and Functional Impact of Parkinson Disease-Associated Mutations in the E3 Ubiquitin Ligase Parkin.Human mutation · 2015Article
- The E3 ubiquitin ligase parkin is recruited to the 26 S proteasome via the proteasomal ubiquitin receptor Rpn13.The Journal of biological chemistry · 2015Article
- Protein recycling pathways in neurodegenerative diseases.Alzheimer's research & therapy · 2014Review
- Structure and Function of Parkin, PINK1, and DJ-1, the Three Musketeers of Neuroprotection.Frontiers in neurology · 2013Article
- Solution structure of the E3 ligase HOIL-1 Ubl domain.Protein science : a publication of the Protein Society · 2012Article
- Autoregulation of Parkin activity through its ubiquitin-like domain.The EMBO journal · 2011Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Autosomal recessive juvenile parkinsonism (ARJP) is an early onset familial form of Parkinson's disease. Approximately 50% of all ARJP cases are attributed to mutations in the gene park2, coding for the protein parkin. Parkin is a multidomain E3 ubiquitin ligase with six distinct domains including an N-terminal ubiquitin-like (Ubl) domain. In this work we examined the structure, stability, and interactions of the parkin Ubl domain containing most ARJP causative mutations. Using NMR spectroscopy we show that the Ubl domain proteins containing the ARJP substitutions G12R, D18N, K32T, R33Q, P37L, and K48A retained a similar three-dimensional fold as the Ubl domain, while at least one other (V15M) had altered packing. Four substitutions (A31D, R42P, A46P, and V56E) result in poor folding of the domain, while one protein (T55I) showed evidence of heterogeneity and aggregation. Further, of the substitutions that maintained their three-dimensional fold, we found that four of these (V15M, K32T, R33Q, and P37L) lead to impaired function due to decreased ability to interact with the 19S regulatory subunit S5a. Three substitutions (G12R, D18N, and Q34R) with an uncertain role in the disease did not alter the three-dimensional fold or S5a interaction. This work provides the first extensive characterization of the structural effects of causative mutations within the ubiquitin-like domain in ARJP.
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