| http://purl.uniprot.org/citations/14607841 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/14607841 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/14607841 | http://www.w3.org/2000/01/rdf-schema#comment | "Mutations in the PARK7/DJ-1 gene cause autosomal-recessive Parkinson's disease. In some patients the gene is deleted. The molecular basis of disease in patients with point mutations is less obvious. We have investigated the molecular properties of [L166P]DJ-1 and the novel variant [E64D]DJ-1. When transfected into non-neuronal and neuronal cell lines, steady-state expression levels of [L166P]DJ-1 were dramatically lower than wild-type [WT]DJ-1 and [E64D]DJ-1. Cycloheximide and pulse-chase experiments revealed that the decreased expression levels of [L166P]DJ-1 were because of accelerated protein turnover. Proteasomal degradation was not the major pathway of DJ-1 breakdown because treatment with the proteasome inhibitor MG-132 caused only minimal accumulation of DJ-1, even of the very unstable [L166P]DJ-1 mutant. Because of the structural resemblance of DJ-1 with bacterial cysteine proteases, we considered an autoproteolytic mechanism. However, neither pharmacological inhibition nor site-directed mutagenesis of the putative active site residue Cys-106 stabilized DJ-1. To gain further insight into the structural defects of DJ-1 mutants, human [WT]DJ-1 and both mutants were expressed in Escherichia coli. As in eukaryotic cells, expression levels of [L166P]DJ-1 were dramatically reduced compared with [WT]DJ-1 and [E64D]DJ-1. Circular dichroism spectrometry revealed that the solution structures of [WT]DJ-1 and [E64D]DJ-1 are rich in beta-strand and alpha-helix conformation. Alpha-helices were more susceptible to thermal denaturation than the beta-sheet, and [WT]DJ-1 was more flexible in this regard than [E64D]DJ-1. Thus, structural defects of [E64D]DJ-1 only become apparent upon denaturing conditions, whereas the L166P mutation causes a drastic defect that leads to excessive degradation."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m309204200"xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m309204200"xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/author | "Beyer K."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/author | "Beyer K."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/author | "Yamamoto A."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/author | "Yamamoto A."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/author | "Haass C."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/author | "Haass C."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/author | "Regula J.T."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/author | "Regula J.T."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/author | "Nuscher B."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/author | "Nuscher B."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/author | "Goerner K."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/author | "Goerner K."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/author | "Holtorf E."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/author | "Holtorf E."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/author | "Kahle P.J."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/author | "Kahle P.J."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/author | "Odoy S."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/author | "Odoy S."xsd:string |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
| http://purl.uniprot.org/citations/14607841 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |