In one paragraphArticle in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
2 · The registryThe 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
3 · Its place in the literatureWho cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
19 authors.
Amalia Villagran SuarezDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.ORCID 0000-0003-3400-2330 Kathryn S HatchDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.
Tatyana BodrugDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.ORCID 0000-0001-9017-962X Wei GaiDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.ORCID 0009-0005-5681-7380 Katherine J SurridgeDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.ORCID 0000-0003-0048-5784 Elizabeth MoussikhinaDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.ORCID 0009-0009-3642-0406 Kendrick Hv NguyenDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.ORCID 0009-0000-1928-6991 Marta Sanz-MurilloDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.ORCID 0000-0002-6175-9315 Robert CallahanDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.
Erica XiongDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.ORCID 0009-0000-8023-5720 Delisa RamosDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.ORCID 0009-0001-4294-0258 Lawrence ZhuDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143.
Verena DedererInstitute of Pharmaceutical Chemistry and Structural Genomics Consortium, Goethe-University Frankfurt am Main, Germany.ORCID 0000-0002-7877-4706 Sebastian MatheaInstitute of Pharmaceutical Chemistry and Structural Genomics Consortium, Goethe-University Frankfurt am Main, Germany.ORCID 0000-0001-8500-4569 Stefan KnappInstitute of Pharmaceutical Chemistry and Structural Genomics Consortium, Goethe-University Frankfurt am Main, Germany.ORCID 0000-0001-5995-6494 Kevan M ShokatDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143.ORCID 0000-0001-8590-7741 Samara L Reck-PetersonDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.ORCID 0000-0002-1553-465X Andres E LeschzinerDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.ORCID 0000-0002-7732-7023 Funding
Molecular Biophysics Training Grant at UC San DiegoT32GM139795 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Galia Debelouchina, ELIZABETH A. KOMIVES · 2021 to 2026
$3.0MNIGMS NIH HHS T32 GM139795
6 · The paper itselfAbstract
Mutations in Leucine-Rich Repeat Kinase 2 (LRRK2) are the second most common cause of autosomal-dominant Parkinson's disease (PD), and increased LRRK2 kinase activity is also observed in idiopathic PD, making LRRK2 a major actionable therapeutic target. LRRK2 is a 286-kDa multidomain enzyme containing a Ras-like GTPase (ROC) and a kinase domain. Using cryo-EM, biochemical reconstitution, and cell-based assays, we show that the ROC GTPase governs switching between autoinhibited and active states: GTP binding promotes activation, whereas GDP binding enforces autoinhibition. Two common PD-linked mutations, G2019S and R1441C/G/H, activate LRRK2 through distinct structural mechanisms, revealing genotype-specific routes to dysregulation. These findings provide a unified framework for understanding LRRK2 regulation with broad therapeutic implications. Stabilizing the GDP-bound state may inhibit LRRK2 by maintaining autoinhibition, whereas promoting the GTP-bound state could be advantageous in specific cellular contexts, such as the lung, where increased LRRK2 kinase activity may play protective or regulatory roles.
Identifiers
PMID42282830
PMCPMC13252133
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