Structural interface between LRRK2 and 14-3-3 protein
نویسندگان
چکیده
منابع مشابه
14-3-3 proteins are promising LRRK2 interactors.
Mutations in LRRK2 (leucine-rich repeat kinase 2) are the most common cause of familial PD (Parkinson's disease). Mutations that cause PD are found in either the GTPase or kinase domains of LRRK2 or an intervening sequence called the COR [C-terminus of ROC (Ras of complex proteins)] domain. As well as the two catalytic domains, LRRK2 possesses several protein-protein interaction domains, but th...
متن کاملLRRK2 secretion in exosomes is regulated by 14-3-3.
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset Parkinson's disease (PD). Emerging evidence suggests a role for LRRK2 in the endocytic pathway. Here, we show that LRRK2 is released in extracellular microvesicles (i.e. exosomes) from cells that natively express LRRK2. LRRK2 localizes to collecting duct epithelial cells in the kidney that actively secrete exosomes into...
متن کاملDiscovery and structural characterization of a small molecule 14-3-3 protein-protein interaction inhibitor.
The 14-3-3 family of phosphoserine/threonine-recognition proteins engage multiple nodes in signaling networks that control diverse physiological and pathophysiological functions and have emerged as promising therapeutic targets for such diseases as cancer and neurodegenerative disorders. Thus, small molecule modulators of 14-3-3 are much needed agents for chemical biology investigations and the...
متن کاملStructural basis for protein-protein interactions in the 14-3-3 protein family.
The seven members of the human 14-3-3 protein family regulate a diverse range of cell signaling pathways by formation of protein-protein complexes with signaling proteins that contain phosphorylated Ser/Thr residues within specific sequence motifs. Previously, crystal structures of three 14-3-3 isoforms (zeta, sigma, and tau) have been reported, with structural data for two isoforms deposited i...
متن کاملParkinson-related LRRK2 mutation R1441C/G/H impairs PKA phosphorylation of LRRK2 and disrupts its interaction with 14-3-3.
Leucine-rich repeat kinase 2 (LRRK2) is a multidomain protein implicated in Parkinson disease (PD); however, the molecular mechanism and mode of action of this protein remain elusive. cAMP-dependent protein kinase (PKA), along with other kinases, has been suggested to be an upstream kinase regulating LRRK2 function. Using MS, we detected several sites phosphorylated by PKA, including phosphoryl...
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ژورنال
عنوان ژورنال: Biochemical Journal
سال: 2017
ISSN: 0264-6021,1470-8728
DOI: 10.1042/bcj20161078