ArticleProceedings of the National Academy of Sciences of the United States of America2002
Probing protein conformational changes in living cells by using designer binding proteins: application to the estrogen receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 138 citations in OpenAlex.
- Structure prediction of alternative protein conformations.Nature communications · 2024Article
- Bioreversible Anionic Cloaking Enables Intracellular Protein Delivery with Ionizable Lipid Nanoparticles.ACS central science · 2024Article
- Labeling of a mutant estrogen receptor with an Affimer in a breast cancer cell line.Biophysical journal · 2022Article
- Computational approaches to identify a novel binding site of BHPI on estrogen receptor alpha.Steroids · 2022Article
- Monobodies as tool biologics for accelerating target validation and druggable site discovery.RSC medicinal chemistry · 2021Review
- The reduced form of the antibody CH2 domain.Protein science : a publication of the Protein Society · 2021Article
- PEG Linker Improves Antitumor Efficacy and Safety of Affibody-Based Drug Conjugates.International journal of molecular sciences · 2021Article
- Review
- Tunable light and drug induced depletion of target proteins.Nature communications · 2020Article
- Estrogen receptor 1 mutations in 260 cervical cancer samples from Chinese patients.Oncology letters · 2019Article
- The Peptide ERα17p Is a GPER Inverse Agonist that Exerts Antiproliferative Effects in Breast Cancer Cells.Cells · 2019Article
- Review
- Synthetic 10FN3-based mono- and bivalent inhibitors of MDM2/X function.Protein engineering, design & selection : PEDS · 2018Article
- Generating FN3-Based Affinity Reagents Through Phage Display.Current protocols in chemical biology · 2018Article
- Identification by Molecular Docking ofHomoisoflavones from Leopoldia comosa as Ligands of Estrogen Receptors.Molecules (Basel, Switzerland) · 2018Article
- Design and Functional Characterization of Synthetic E3 Ubiquitin Ligases for Targeted Protein Depletion.Current protocols in chemical biology · 2018Article
- Monobodies and other synthetic binding proteins for expanding protein science.Protein science : a publication of the Protein Society · 2017Review
- Quantifying Hormone Disruptors with an Engineered Bacterial Biosensor.ACS central science · 2017Article
- RasIns: Genetically Encoded Intrabodies of Activated Ras Proteins.Journal of molecular biology · 2017Article
- A Conjugate Based on Anti-HER2 Diaffibody and Auristatin E Targets HER2-Positive Cancer Cells.International journal of molecular sciences · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
A challenge in understanding the mechanism of protein function in biology is to establish the correlation between functional form in the intracellular environment and high-resolution structures obtained with in vitro techniques. Here we present a strategy to probe conformational changes of proteins inside cells. Our method involves: (i) engineering binding proteins to different conformations of a target protein, and (ii) using them to sense changes in the surface property of the target in cells. We probed ligand-induced conformational changes of the estrogen receptor alpha (ER alpha) ligand-binding domain (LBD). By using yeast two-hybrid techniques, we first performed combinatorial library screening of "monobodies" (small antibody mimics using the scaffold of a fibronectin type III domain) for clones that bind to ER alpha and then characterized their interactions with ER alpha in the nucleus, the native environment of ER alpha, in the presence of various ligands. A library using a highly flexible loop yielded monobodies that specifically recognize a particular ligand complex of ER alpha, and the pattern of monobody specificity was consistent with the structural differences found in known crystal structures of ER alpha-LBD. A more restrained loop library yielded clones that bind both agonist- and antagonist-bound ER alpha. Furthermore, we found that a deletion of the ER alpha F domain that is C-terminally adjacent to the LBD increased the crossreactivity of monobodies to the apo-ER alpha-LBD, suggesting a dynamic nature of the ER alpha-LBD conformation and a role of the F domain in restraining the LBD in an inactive conformation.
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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.