ArticleEMBO reports2021
Structural basis for the specificity of PPM1H phosphatase for Rab GTPases.
Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- LRRK2: Molecular Mechanisms in Parkinson's Disease.International journal of molecular sciences · 2026Review
- PHLPP is neither a Phosphatase nor a Tumor Suppressor.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- The structural basis for LRRK2's activation and autoinhibition.bioRxiv : the preprint server for biology · 2026Article
- Phosphosite-specific co-regulation networks of MELK kinase: insights from integrative global phosphoproteomes.Journal, genetic engineering & biotechnology · 2026Article
- AlphaFold as a prior: experimental structure determination conditioned on a pretrained neural network.Nature methods · 2026Article
- Selectivity profiles and substrate recognition of Rab-phosphorylating kinases.The Biochemical journal · 2025Article
- PPM1M, an LRRK2-counteracting, phosphoRab12-preferring phosphatase with a potential link to Parkinson's disease.Cell reports · 2025Article
- PHLPP2 is a pseudophosphatase that lost activity in the metazoan ancestor.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Salmonella exploits LRRK2-dependent plasma membrane dynamics to invade host cells.Nature communications · 2025Article
- Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Docking interactions determine substrate specificity of members of a widespread family of protein phosphatases.The Journal of biological chemistry · 2024Article
- Article
- Loss of primary cilia and dopaminergic neuroprotection in pathogenic LRRK2-driven and idiopathic Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Loss of primary cilia and dopaminergic neuroprotection in pathogenic LRRK2-driven and idiopathic Parkinson's disease.bioRxiv : the preprint server for biology · 2024Article
- Parkinson's VPS35[D620N] mutation induces LRRK2-mediated lysosomal association of RILPL1 and TMEM55B.Science advances · 2023Article
- Localization of PPM1H phosphatase tunes Parkinson's disease-linked LRRK2 kinase-mediated Rab GTPase phosphorylation and ciliogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Review
- Structural basis for the specificity of PPM1H phosphatase for Rab GTPases.EMBO reports · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
LRRK2 serine/threonine kinase is associated with inherited Parkinson's disease. LRRK2 phosphorylates a subset of Rab GTPases within their switch 2 motif to control their interactions with effectors. Recent work has shown that the metal-dependent protein phosphatase PPM1H counteracts LRRK2 by dephosphorylating Rabs. PPM1H is highly selective for LRRK2 phosphorylated Rabs, and closely related PPM1J exhibits no activity towards substrates such as Rab8a phosphorylated at Thr72 (pThr72). Here, we have identified the molecular determinant of PPM1H specificity for Rabs. The crystal structure of PPM1H reveals a structurally conserved phosphatase fold that strikingly has evolved a 110-residue flap domain adjacent to the active site. The flap domain distantly resembles tudor domains that interact with histones in the context of epigenetics. Cellular assays, crosslinking and 3-D modelling suggest that the flap domain encodes the docking motif for phosphorylated Rabs. Consistent with this hypothesis, a PPM1J chimaera with the PPM1H flap domain dephosphorylates pThr72 of Rab8a both in vitro and in cellular assays. Therefore, PPM1H has acquired a Rab-specific interaction domain within a conserved phosphatase fold.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.