ArticleProceedings of the National Academy of Sciences of the United States of America2019
Mechanism for autoinhibition and activation of the MORC3 ATPase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- MORC3 represses a tandem repeat enhancer to regulate interferon.The EMBO journal · 2026Article
- SUMO operates from a unique long tandem repeat to keep innate immunity in check.Nucleic acids research · 2025Article
- MORC2 is a phosphorylation-dependent DNA compaction machine.Nature communications · 2025Article
- Identification and characterization of a human MORC2 DNA binding region that is required for gene silencing.Nucleic acids research · 2025Article
- VCP/p97-associated proteins are binders and debranching enzymes of K48-K63-branched ubiquitin chains.Nature structural & molecular biology · 2024Article
- Oligomerization and a distinct tRNA-binding loop are important regulators of human arginyl-transferase function.Nature communications · 2024Article
- Identification and characterization of a human MORC2 DNA binding region that is required for gene silencing.bioRxiv : the preprint server for biology · 2024Article
- Oncogenic MORC2 in cancer development and beyond.Genes & diseases · 2024Review
- Article
- Research progress on the dermatomyositis specific autoantibodies and malignancy associated dermatomyositis.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- MORC3 represses the HCMV major immediate early promoter in myeloid cells in the absence of PML nuclear bodies.Journal of medical virology · 2023Article
- Structural Investigations of Interactions between the Influenza a Virus NS1 and Host Cellular Proteins.Viruses · 2023Review
- The structural basis of tRNA recognition by arginyl-tRNA-protein transferase.Nature communications · 2023Article
- Differentially expressed liver exosome-related genes as candidate prognostic biomarkers for hepatocellular carcinoma.Annals of translational medicine · 2022Article
- Binding Specificity of ASHH2 CW Domain Toward H3K4me1 Ligand Is Coupled to Its Structural Stability Through Its α1-Helix.Frontiers in molecular biosciences · 2022Article
- Mechanistic similarities in recognition of histone tails and DNA by epigenetic readers.Current opinion in structural biology · 2021Review
- MORC protein family-related signature within human disease and cancer.Cell death & disease · 2021Review
- The role of MORC3 in silencing transposable elements in mouse embryonic stem cells.Epigenetics & chromatin · 2021Article
- Morc3 silences endogenous retroviruses by enabling Daxx-mediated histone H3.3 incorporation.Nature communications · 2021Article
- Molecular mechanism of the MORC4 ATPase activation.Nature communications · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Microrchidia 3 (MORC3) is a human protein linked to autoimmune disorders, Down syndrome, and cancer. It is a member of a newly identified family of human ATPases with an uncharacterized mechanism of action. Here, we elucidate the molecular basis for inhibition and activation of MORC3. The crystal structure of the MORC3 region encompassing the ATPase and CW domains in complex with a nonhydrolyzable ATP analog demonstrates that the two domains are directly coupled. The extensive ATPase:CW interface stabilizes the protein fold but inhibits the catalytic activity of MORC3. Enzymatic, NMR, mutational, and biochemical analyses show that in the autoinhibited, off state, the CW domain sterically impedes binding of the ATPase domain to DNA, which in turn is required for the catalytic activity. MORC3 autoinhibition is released by disrupting the intramolecular ATPase:CW coupling through the competitive interaction of CW with histone H3 tail or by mutating the interfacial residues. Binding of CW to H3 leads to a marked rearrangement in the ATPase-CW cassette, which frees the DNA-binding site in active MORC3 (on state). We show that ATP-induced dimerization of the ATPase domain is strictly required for the catalytic activity and that the dimeric form of ATPase-CW might cooperatively bind to dsDNA. Together, our findings uncovered a mechanism underlying the fine-tuned regulation of the catalytic domain of MORC3 by the epigenetic reader, CW.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.