ArticleStructure (London, England : 1993)2017
Achieving a Graded Immune Response: BTK Adopts a Range of Active/Inactive Conformations Dictated by Multiple Interdomain Contacts.
Article in Structure (London, England : 1993), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Two-step mechanism of Bruton's tyrosine kinase membrane recruitment and activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- More than an attachment module: covalent inhibitor warheads influence BTK dynamics and function.bioRxiv : the preprint server for biology · 2026Article
- Mechanism of activation of an ancestral TEC kinase by PIPNpj structural biology · 2026Article
- Two-Step Mechanism of Bruton's Tyrosine Kinase Membrane Recruitment and Activation.bioRxiv : the preprint server for biology · 2025Article
- BTK autoinhibition analyzed by high-throughput swaps of SH2 domains.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Membrane-dependent assembly of Bruton's tyrosine kinase mediated by the Proline-rich region and SH3 domain.Protein science : a publication of the Protein Society · 2025Article
- Article
- Exploring 2-Sulfonylpyrimidine Warheads as Acrylamide Surrogates for Targeted Covalent Inhibition: A BTK Story.Journal of medicinal chemistry · 2024Article
- Article
- Bruton's Tyrosine Kinase Inhibitors with Distinct Binding Modes Reveal Differential Functional Impact on B-Cell Receptor Signaling.Molecular cancer therapeutics · 2024Article
- Screening and Characterization of Allosteric Small Molecules Targeting Bruton's Tyrosine Kinase.Biochemistry · 2024Article
- PON-Fold: Prediction of Substitutions Affecting Protein Folding Rate.International journal of molecular sciences · 2023Article
- Stimulation of the catalytic activity of the tyrosine kinase Btk by the adaptor protein Grb2.eLife · 2023Article
- BTK Isoforms p80 and p65 Are Expressed in Head and Neck Squamous Cell Carcinoma (HNSCC) and Involved in Tumor Progression.Cancers · 2023Article
- Regulatory mechanisms triggered by enzyme interactions with lipid membrane surfaces.Frontiers in molecular biosciences · 2023Review
- ATP-site inhibitors induce unique conformations of the acute myeloid leukemia-associated Src-family kinase, Fgr.Structure (London, England : 1993) · 2022Article
- Comparison of Intermolecular Interactions of Irreversible and Reversible Inhibitors with Bruton's Tyrosine Kinase via Molecular Dynamics Simulations.Molecules (Basel, Switzerland) · 2022Article
- The HIV-1 protein Nef activates the Tec family kinase Btk by stabilizing an intermolecular SH3-SH2 domain interaction.Science signaling · 2022Article
- The Conformational State of the BTK Substrate PLCγ Contributes to Ibrutinib Resistance.Journal of molecular biology · 2022Article
- BTK, the new kid on the (oncology) block?Frontiers in oncology · 2022Review
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Abstract
Capturing the functionally relevant forms of dynamic, multidomain proteins is extremely challenging. Bruton's tyrosine kinase (BTK), a kinase essential for B and mast cell function, has stubbornly resisted crystallization in its full-length form. Here, nuclear magnetic resonance and hydrogen-deuterium exchange mass spectrometry show that BTK adopts a closed conformation in dynamic equilibrium with open, active conformations. BTK lacks the phosphotyrosine regulatory tail of the SRC kinases, yet nevertheless achieves a phosphotyrosine-independent C-terminal latch. The unique proline-rich region is an internal "on" switch pushing the autoinhibited kinase toward its active state. Newly identified autoinhibitory contacts in the BTK pleckstrin homology domain are sensitive to phospholipid binding, which induces large-scale allosteric changes. The multiplicity of these regulatory contacts suggests a clear mechanism for gradual or "analog" kinase activation as opposed to a binary "on/off" switch. The findings illustrate how previously modeled information for recalcitrant full-length proteins can be expanded and validated with a convergent multidisciplinary experimental approach.
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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.