دورية أكاديمية
LRRK2 Structure-Based Activation Mechanism and Pathogenesis
| العنوان: | LRRK2 Structure-Based Activation Mechanism and Pathogenesis |
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| المؤلفون: | Zhang, Xiaojuan, Kortholt, Arjan |
| المصدر: | Zhang , X & Kortholt , A 2023 , ' LRRK2 Structure-Based Activation Mechanism and Pathogenesis ' , Biomolecules , vol. 13 , no. 4 , 612 . https://doi.org/10.3390/biom13040612Test |
| سنة النشر: | 2023 |
| المجموعة: | University of Groningen research database |
| الوصف: | Mutations in the multidomain protein Leucine-rich-repeat kinase 2 (LRRK2) have been identified as a genetic risk factor for both sporadic and familial Parkinson’s disease (PD). LRRK2 has two enzymatic domains: a RocCOR tandem with GTPase activity and a kinase domain. In addition, LRRK2 has three N-terminal domains: ARM (Armadillo repeat), ANK (Ankyrin repeat), and LRR (Leucine-rich-repeat), and a C-terminal WD40 domain, all of which are involved in mediating protein– protein interactions (PPIs) and regulation of the LRRK2 catalytic core. The PD-related mutations have been found in nearly all LRRK2 domains, and most of them have increased kinase activity and/or decreased GTPase activity. The complex activation mechanism of LRRK2 includes at least intramolecular regulation, dimerization, and membrane recruitment. In this review, we highlight the recent developments in the structural characterization of LRRK2 and discuss these developments from the perspective of the LRRK2 activation mechanism, the pathological role of the PD mutants, and therapeutic targeting. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://research.rug.nl/en/publications/3dffab0f-5feb-44b8-b27e-e4ee1798ec38Test |
| DOI: | 10.3390/biom13040612 |
| الإتاحة: | https://doi.org/10.3390/biom13040612Test https://hdl.handle.net/11370/3dffab0f-5feb-44b8-b27e-e4ee1798ec38Test https://research.rug.nl/en/publications/3dffab0f-5feb-44b8-b27e-e4ee1798ec38Test https://pure.rug.nl/ws/files/625563821/biomolecules_13_00612_v2.pdfTest https://www.mdpi.com/2218-273X/13/4/612Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.73EABA81 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/biom13040612 |
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