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Interplay Between LRRK2 GTPase and Kinase Domains

Takens, Carsten, C. (2021) Interplay Between LRRK2 GTPase and Kinase Domains. Bachelor's Thesis, Life Science and Technology.

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Abstract

Mutations in leucine-rich repeat-kinase 2 (LRRK2) are a common cause of both familial and sporadic forms of Parkinson’s disease (PD). LRRK2 is a large, irregular protein featuring both a kinase and a Ras of complex (Roc) GTPase domain. While these domains can interact in separate proteins, the interplay between the Roc and kinase domain of LRRK2 is still under debate. In this thesis, I delved into the structure and function of both domains, and aimed to find out if there is interplay between them. I found several lines of evidence suggesting interplay between both domains, including effects of GTP binding on LRRK2 dimerisation and kinase activity, phosphorylation of the Roc domain by the kinase domain, and effects of GTP hydrolysis on kinase activity. A deeper understanding of the complex regulatory interactions of LRRK2 Roc and kinase domains will contribute to our understanding of LRRK2 regulation, and will therefore be invaluable for selective pharmaceutical intervention of PD.

Item Type: Thesis (Bachelor's Thesis)
Supervisor name: Kortholt, A. and Scheffers, D.J.
Degree programme: Life Science and Technology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 02 Aug 2021 14:39
Last Modified: 02 Aug 2021 14:39
URI: https://fse.studenttheses.ub.rug.nl/id/eprint/25565

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