| http://purl.uniprot.org/citations/34107286 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34107286 | http://www.w3.org/2000/01/rdf-schema#comment | "Mutations in leucine-rich repeat kinase 2 (LRRK2) are commonly implicated in the pathogenesis of both familial and sporadic Parkinson's disease (PD). LRRK2 regulates critical cellular processes at membranous organelles and forms microtubule-based pathogenic filaments, yet the molecular basis underlying these biological roles of LRRK2 remains largely enigmatic. Here, we determined high-resolution structures of full-length human LRRK2, revealing its architecture and key interdomain scaffolding elements for rationalizing disease-causing mutations. The kinase domain of LRRK2 is captured in an inactive state, a conformation also adopted by the most common PD-associated mutation, LRRK2G2019S. This conformation serves as a framework for structure-guided design of conformational specific inhibitors. We further determined the structure of COR-mediated LRRK2 dimers and found that single-point mutations at the dimer interface abolished pathogenic filamentation in cells. Overall, our study provides mechanistic insights into physiological and pathological roles of LRRK2 and establishes a structural template for future therapeutic intervention in PD."xsd:string |
| http://purl.uniprot.org/citations/34107286 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.cell.2021.05.004"xsd:string |
| http://purl.uniprot.org/citations/34107286 | http://purl.uniprot.org/core/author | "Peng J."xsd:string |
| http://purl.uniprot.org/citations/34107286 | http://purl.uniprot.org/core/author | "Sun J."xsd:string |
| http://purl.uniprot.org/citations/34107286 | http://purl.uniprot.org/core/author | "Zhu H."xsd:string |
| http://purl.uniprot.org/citations/34107286 | http://purl.uniprot.org/core/author | "Yu K."xsd:string |
| http://purl.uniprot.org/citations/34107286 | http://purl.uniprot.org/core/author | "Xie B."xsd:string |
| http://purl.uniprot.org/citations/34107286 | http://purl.uniprot.org/core/author | "Pitre A."xsd:string |
| http://purl.uniprot.org/citations/34107286 | http://purl.uniprot.org/core/author | "Hixson P."xsd:string |
| http://purl.uniprot.org/citations/34107286 | http://purl.uniprot.org/core/author | "Myasnikov A."xsd:string |
| http://purl.uniprot.org/citations/34107286 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/34107286 | http://purl.uniprot.org/core/name | "Cell"xsd:string |
| http://purl.uniprot.org/citations/34107286 | http://purl.uniprot.org/core/pages | "3519-3527.e10"xsd:string |
| http://purl.uniprot.org/citations/34107286 | http://purl.uniprot.org/core/title | "Structural analysis of the full-length human LRRK2."xsd:string |
| http://purl.uniprot.org/citations/34107286 | http://purl.uniprot.org/core/volume | "184"xsd:string |
| http://purl.uniprot.org/citations/34107286 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34107286 |
| http://purl.uniprot.org/citations/34107286 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/34107286 |
| http://purl.uniprot.org/uniprot/#_A0A218N881-mappedCitation-34107286 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34107286 |
| http://purl.uniprot.org/uniprot/#_A2VED2-mappedCitation-34107286 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34107286 |
| http://purl.uniprot.org/uniprot/#_Q17RV3-mappedCitation-34107286 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34107286 |
| http://purl.uniprot.org/uniprot/#_Q6MZN9-mappedCitation-34107286 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34107286 |
| http://purl.uniprot.org/uniprot/#_Q5S007-mappedCitation-34107286 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34107286 |
| http://purl.uniprot.org/uniprot/A0A218N881 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/34107286 |
| http://purl.uniprot.org/uniprot/Q5S007 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/34107286 |