ArticleProceedings of the National Academy of Sciences of the United States of America2014
Membrane-enabled dimerization of the intrinsically disordered cytoplasmic domain of ADAM10.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Multimodal activity-affinity assay of ADAM-10 extracellular vesicles in untreated plasma reveals metastatic stage of colorectal cancer.Biosensors & bioelectronics · 2026Article
- Review
- ADAM Proteases in Cancer: Biological Roles, Therapeutic Challenges, and Emerging Opportunities.Cancers · 2025Review
- Identifying Transmembrane Interactions in Receptor Protein Tyrosine Phosphatase Homodimerization and Heterodimerization.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Inducing prion protein shedding as a neuroprotective and regenerative approach in pathological conditions of the brain: from theory to facts.Neural regeneration research · 2023Review
- Promoting the activity of a receptor tyrosine phosphatase with a novel pH-responsive transmembrane agonist inhibits cancer-associated phenotypes.Protein science : a publication of the Protein Society · 2023Article
- ADAM10-a "multitasker" in sepsis: focus on its posttranslational target.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- A Bioengineering Strategy to Control ADAM10 Activity in Living Cells.International journal of molecular sciences · 2023Article
- ADAM10 Site-Dependent Biology: Keeping Control of a Pervasive Protease.International journal of molecular sciences · 2021Review
- The Structural and Functional Diversity of Intrinsically Disordered Regions in Transmembrane Proteins.The Journal of membrane biology · 2019Review
- Functions of 'A disintegrin and metalloproteases (ADAMs)' in the mammalian nervous system.Cellular and molecular life sciences : CMLS · 2019Review
- The emerging role of ADAM metalloproteinases in immunity.Nature reviews. Immunology · 2018Review
- Levels of ADAM10 are reduced in Alzheimer's disease CSF.Journal of neuroinflammation · 2018Article
- Recent advances in the pathogenetic mechanisms of sepsis-associated acute kidney injury.Journal of nephrology · 2018Review
- Functions of intrinsic disorder in transmembrane proteins.Cellular and molecular life sciences : CMLS · 2017Review
- Regulation of A disintegrin and metalloproteinase (ADAM) family sheddases ADAM10 and ADAM17: The emerging role of tetraspanins and rhomboids.Platelets · 2017Review
- Transitional B cells commit to marginal zone B cell fate by Taok3-mediated surface expression of ADAM10.Nature immunology · 2017Article
- Regulation of Alpha-Secretase ADAM10Frontiers in molecular neuroscience · 2017Review
- Activation of cell-surface proteases promotes necroptosis, inflammation and cell migration.Cell research · 2016Article
- Reduced Proteolytic Shedding of Receptor Tyrosine Kinases Is a Post-Translational Mechanism of Kinase Inhibitor Resistance.Cancer discovery · 2016Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Intrinsically disordered protein regions are widely distributed in the cytoplasmic domains of many transmembrane receptors. The cytoplasmic domain of a disintegrin and metalloprotease (ADAM)10, a transmembrane metalloprotease mediating ectodomain shedding of diverse membrane proteins, was recently suggested to mediate the homodimerization of ADAM10. Here we show that a recombinant cytoplasmic domain of ADAM10 (A10Cp) is unstructured as judged by its susceptibility to limited trypsin digestion and its circular dichroism spectrum. In comparison, recombinant transmembrane-cytoplasmic domain of ADAM10 (A10TmCp) reconstituted in dodecylphosphocholine (DPC) micelles exhibits much greater resistance to trypsin digestion, with its cytoplasmic domain taking on a significant ordered structure. FRET analysis demonstrates that, although A10Cp remains monomeric, A10TmCp forms a tight homodimer (K(d) ∼ 7 nM) in DPC micelles. Phospholipid-conjugated A10Cp dose-dependently inhibits formation of A10TmCp homodimer, whereas A10Cp achieves only limited inhibition. Placing the transmembrane and cytoplasmic domains of ADAM10, but not the transmembrane domain alone, in their native orientation in the inner membrane of Escherichia coli produces specific and strong dimerization signal in the AraC-based transcriptional reporter assay. A chimeric construct containing the otherwise monomeric transmembrane domain of L-selectin and the cytoplasmic domain of ADAM10 produces a similar dimerization signal. Overall, these results demonstrate that a transmembrane domain imparts a stable structure to the adjacent and intrinsically disordered cytoplasmic domain of ADAM10 to form a homodimer in the membrane. This finding advances our understanding of the regulatory mechanism of ADAMs and has general implications for membrane-protein interactions in the process of transmembrane signaling.
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