ArticleMolecular cell2007
Proline cis-trans isomerization controls autoinhibition of a signaling protein.
Article in Molecular cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 185 citations in OpenAlex.
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- A tethering mechanism underlies Pin1-catalyzed prolineProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mechanically weak and highly dynamic state of mechanosensitive titin Ig domains induced by proline isomerization.Nature communications · 2025Article
- ProlineJournal of the American Chemical Society · 2025Article
- Phi-Value and NMR Structural Analysis of a Coupled Native-State Prolyl Isomerization and Conformational Protein Folding Process.Biomolecules · 2025Article
- Temperature-dependent fold-switching mechanism of the circadian clock protein KaiB.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2.Nature communications · 2024Article
- The Cyclophilin Inhibitor Rencofilstat Decreases HCV-Induced Hepatocellular Carcinoma Independently of Its Antiviral Activity.Viruses · 2023Article
- Cyclophilin A associates with and regulates the activity of ZAP70 in TCR/CD3-stimulated T cells.Cellular and molecular life sciences : CMLS · 2022Article
- SelectiveAngewandte Chemie (International ed. in English) · 2022Article
- Immuno-dominant dengue NS1 peptides as antigens for production of monoclonal antibodies.Frontiers in molecular biosciences · 2022Article
- Protein yoga: Conformational versatility of the Hemolysin II C-terminal domain detailed by NMR structures for multiple states.Protein science : a publication of the Protein Society · 2021Article
- A Proline-Based Tectons and Supramolecular Synthons for Drug Design 2.0: A Case Study of ACEI.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Investigation of theRSC advances · 2020Article
- CrkL is required for donor T cell migration to GvHD target organs.Oncotarget · 2020Article
- The (un)structural biology of biomolecular liquid-liquid phase separation using NMR spectroscopy.The Journal of biological chemistry · 2020Review
- Phosphorylation-Dependent Pin1 Isomerization of ATR: Its Role in Regulating ATR's Anti-apoptotic Function at Mitochondria, and the Implications in Cancer.Frontiers in cell and developmental biology · 2020Review
- Monitoring the stabilities of a mixture of peptides by mass-spectrometry-based techniques.European journal of mass spectrometry (Chichester, England) · 2019Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
Autoinhibition is being widely used in nature to repress otherwise constitutive protein activities and is typically regulated by extrinsic factors. Here we show that autoinhibition can be controlled by an intrinsic intramolecular switch afforded by prolyl cis-trans isomerization. We find that a proline on the linker tethering the two SH3 domains of the Crk adaptor protein interconverts between the cis and trans conformation. In the cis conformation, the two SH3 domains interact intramolecularly, thereby forming the basis of an autoinhibitory mechanism. Conversely, in the trans conformation Crk exists in an extended, uninhibited conformation that is marginally populated but serves to activate the protein upon ligand binding. Interconversion between the cis and trans, and, hence, of the autoinhibited and activated conformations, is accelerated by the action of peptidyl-prolyl isomerases. Proline isomerization appears to make an ideal switch that can regulate the kinetics of activation, thereby modulating the dynamics of signal response.
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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.