{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Reimer JM"],"funding":["NIGMS NIH HHS"],"pagination":["1735-1745"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10643122"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["30(11)"],"pubmed_abstract":["Leucine Rich Repeat Kinase 1 and 2 (LRRK1 and LRRK2) are homologs in the ROCO family of proteins in humans. Despite their shared domain architecture and involvement in intracellular trafficking, their disease associations are strikingly different: LRRK2 is involved in familial Parkinson's disease while LRRK1 is linked to bone diseases. Furthermore, Parkinson's disease-linked mutations in LRRK2 are typically autosomal dominant gain-of-function while those in LRRK1 are autosomal recessive loss-of-function. Here, to understand these differences, we solved cryo-EM structures of LRRK1 in its monomeric and dimeric forms. Both differ from the corresponding LRRK2 structures. Unlike LRRK2, which is sterically autoinhibited as a monomer, LRRK1 is sterically autoinhibited in a dimer-dependent manner."],"journal":["Nature structural & molecular biology"],"pubmed_title":["Structure of LRRK1 and mechanisms of autoinhibition and activation."],"pmcid":["PMC10643122"],"funding_grant_id":["R35 GM133633"],"pubmed_authors":["Knapp S","Dickey AM","Lin YX","Mathea S","Leschziner AE","Fay EJ","Reck-Peterson SL","Abrisch RG","Reimer JM","Chatterjee D","Daugherty MD"],"additional_accession":[]},"is_claimable":false,"name":"Structure of LRRK1 and mechanisms of autoinhibition and activation.","description":"Leucine Rich Repeat Kinase 1 and 2 (LRRK1 and LRRK2) are homologs in the ROCO family of proteins in humans. Despite their shared domain architecture and involvement in intracellular trafficking, their disease associations are strikingly different: LRRK2 is involved in familial Parkinson's disease while LRRK1 is linked to bone diseases. Furthermore, Parkinson's disease-linked mutations in LRRK2 are typically autosomal dominant gain-of-function while those in LRRK1 are autosomal recessive loss-of-function. Here, to understand these differences, we solved cryo-EM structures of LRRK1 in its monomeric and dimeric forms. Both differ from the corresponding LRRK2 structures. Unlike LRRK2, which is sterically autoinhibited as a monomer, LRRK1 is sterically autoinhibited in a dimer-dependent manner.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Nov","modification":"2026-07-14T19:18:00.817Z","creation":"2025-04-04T07:24:26.449Z"},"accession":"S-EPMC10643122","cross_references":{"pubmed":["37857821"],"doi":["10.1038/s41594-023-01109-1"]}}