{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["300(7)"],"submitter":["Dederer V"],"funding":["Structural Genomics Consortium","Innovative Medicines Initiative","Howard Hughes Medical Institute","Aligning Science Across Parkinson's"],"pubmed_abstract":["Leucine rich repeat kinase 2 (LRRK2) is a large multidomain protein containing two catalytic domains, a kinase and a GTPase, as well as protein interactions domains, including a WD40 domain. The association of increased LRRK2 kinase activity with both the familial and sporadic forms of Parkinson's disease has led to an intense interest in determining its cellular function. However, small molecule probes that can bind to LRRK2 and report on or affect its cellular activity are needed. Here, we report the identification and characterization of the first high-affinity LRRK2-binding designed ankyrin-repeat protein (DARPin), named E11. Using cryo-EM, we show that DARPin E11 binds to the LRRK2 WD40 domain. LRRK2 bound to DARPin E11 showed improved behavior on cryo-EM grids, resulting in higher re"],"journal":["The Journal of biological chemistry"],"pagination":["107469"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11284679"],"repository":["biostudies-literature"],"pubmed_title":["A designed ankyrin-repeat protein that targets Parkinson's disease-associated LRRK2."],"pmcid":["PMC11284679"],"pubmed_authors":["Knapp S","Pluckthun A","Mathea S","Dreier B","Reck-Peterson SL","Nguyen LV","Versees W","Chatterjee D","Hatch KS","Dederer V","Sanz Murillo M","Leschziner AE","Galicia C","Karasmanis EP","Preuss F","Abdul Azeez KR"],"additional_accession":[]},"is_claimable":false,"name":"A designed ankyrin-repeat protein that targets Parkinson's disease-associated LRRK2.","description":"Leucine rich repeat kinase 2 (LRRK2) is a large multidomain protein containing two catalytic domains, a kinase and a GTPase, as well as protein interactions domains, including a WD40 domain. The association of increased LRRK2 kinase activity with both the familial and sporadic forms of Parkinson's disease has led to an intense interest in determining its cellular function. However, small molecule probes that can bind to LRRK2 and report on or affect its cellular activity are needed. Here, we report the identification and characterization of the first high-affinity LRRK2-binding designed ankyrin-repeat protein (DARPin), named E11. Using cryo-EM, we show that DARPin E11 binds to the LRRK2 WD40 domain. LRRK2 bound to DARPin E11 showed improved behavior on cryo-EM grids, resulting in higher re","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jul","modification":"2026-06-01T22:11:25.644Z","creation":"2026-05-22T03:07:36.183Z"},"accession":"S-EPMC11284679","cross_references":{"pubmed":["38876305"],"doi":["10.1016/j.jbc.2024.107469"]}}