Cryo-EM structure of the agonist-bound Hsp90-XAP2-AHR cytosolic complex
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Abstract
The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates a broad spectrum of (patho)physiological processes in response to numerous substances including pollutants, natural products and metabolites. However, the scarcity of structural data precludes understanding of how AHR is activated by such diverse compounds. Our 2.85 Å structure of the human indirubin-bound AHR complex with the chaperone Hsp90 and the co-chaperone XAP2, reported herein, reveals a closed conformation Hsp90 dimer with AHR threaded through its lumen and XAP2 serving as a brace. Importantly, we disclose the long-awaited structure of the AHR PAS-B domain revealing a unique organisation of the ligand-binding pocket and the structural determinants of ligand-binding specificity and promiscuity of the receptor. By providing structural details of the molecular initiating event leading to AHR activation, our study rationalises almost forty years of biochemical data and provides a framework for future mechanistic studies and structure-guided drug design.
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Comparisons among the chaperone-bound states and the ligand-bound, chaperone-free heterodimeric complex revealed that the DE-loop of the AHR PAS-B domain undergoes a conformational change towards the pocket upon ligand binding.
“Comparisons among these three states initially revealed that the DE-loop, situated between Dα and Eα of the AHR PAS-B domain, undergoes a conformational change towards the pocket upon ligand binding29,30 (Fig. 5a).”
From Structural basis for the ligand-dependent activation of heterodimeric AHR-ARNT complex (2025) · cites this paper as [29]
The Results section (‘Exploring AHR ligand-binding mechanism’; page unavailable) reports that indirubin stabilizes the bound PAS-B conformation and reduces mobility in helices Cα and Dα and the Gβ–Hβ loop. The Discussion proposes ligand-induced conformational changes in AHR. Neither passage reports a three-state structural comparison or shows the DE-loop moving toward the pocket. (LLM, conf=0.82)
Experimental — accuracy not yet measuredCompared to two recently published structures of AHR cytosolic complexes bound to Indirubin and BaP, these two ligands demonstrate similar binding patterns within the AHR-ARNT complexes.
“Notably, compared to two recently published structures of AHR cytosolic complexes bound to Indirubin and BaP29,40, these two ligands demonstrate similar binding patterns within the AHR-ARNT complexes (Supplementary Fig. 7g, h)”
From Structural basis for the ligand-dependent activation of heterodimeric AHR-ARNT complex (2025) · cites this paper as [29]
In the cytosolic AHR-HSP90-XAP2 complex, the AHR PAS-B C-ter loop primarily interacts with XAP2.
“Previous studies have indicated that in the cytosolic AHR-HSP90-XAP2 complex29, this loop primarily interacts with XAP2 (Supplementary Fig. 9d).”
From Structural basis for the ligand-dependent activation of heterodimeric AHR-ARNT complex (2025) · cites this paper as [29]
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InfluentialCryo-EM structure of the cytosolic AhR complex.
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“Structurally, AhR contains a bHLH domain and two repeats of a PAS domain, known as PAS-A and PAS-B [45–47] (Fig.”
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MethodMixture Effects of Tryptophan Intestinal Microbial Metabolites on Aryl Hydrocarbon Receptor Activity
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Baischew, A., Engel, S., Taubert, M. C., Geiger, T. M., & Hausch, F. (2023) · Nature Structural & Molecular Biology · doi:10.1038/s41594-023-01098-1 · Cited by 22 · see citing works
“Despite substantial recent structural advances in Hsp90-mediated nuclear hormone maturation 15–19 , a detailed mechanistic understanding of the key steps of GR regulation by the large FKBP co-chaperones has remained elusive, in part owing to difficulties in purifying or functionally reconstituting…”
Miret, N., Pontillo, C. A., Buján, S., Chiappini, F., & Randi, A. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115773 · Cited by 20 · see citing works
Agonist-dependent action of the juvenile hormone receptor
Jindra, M., Tumova, S., Bittova, L., Tůma, R., & Sedlák, D. (2024) · Current Opinion in Insect Science · doi:10.1016/j.cois.2024.101234 · Cited by 21 · see citing works
Finci, L. I., Chakrabarti, M., Gülten, G., Finney, J., Grose, C., Fox, T. L., Yang, R., Nissley, D. V., McCormick, F. P., Esposito, D., et al. (2024) · Communications Biology · doi:10.1038/s42003-024-05959-3 · Cited by 19 · see citing works
Aryl Hydrocarbon Receptor in Health and Disease
Li, H., Fan, Y., Liu, J., Dong, S., Wen, B., Zhang, Y., Wang, X., Duan, X., Hu, Y., Yan, Z., et al. (2025) · MedComm · doi:10.1002/mco2.70426 · Cited by 21 · see citing works
“The kinetic changes associated with AhR activation have been elucidated through the application of split NanoBiT technology and cryo-electron microscopy [252, 253].”
Role of Hepatic Aryl Hydrocarbon Receptor in Non-Alcoholic Fatty Liver Disease
Patil, N. Y., Friedman, J. E., & Joshi, A. (2023) · Receptors · doi:10.3390/receptors2010001 · Cited by 17 · see citing works
Daffern, N., & Radhakrishnan, I. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168370 · Cited by 17 · see citing works
Costs of molecular adaptation to the chemical exposome: a focus on xenobiotic metabolism pathways
Tomkiewicz, C., Coumoul, X., Nioche, P., Barouki, R., & Blanc, É. (2024) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2022.0510 · Cited by 16 · see citing works
“Recently the structure of the AhR PAS-B domain in complex to HsP90 and XAP2 was obtained using cryo-electronic microscopy, paving the way for additional understanding of the mechanisms of ligand binding and activation [46].”
MethodThe aryl hydrocarbon receptor as a tumor modulator: mechanisms to therapy
Chaudhry, K. A., & Bianchi, A. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1375905 · Cited by 15 · see citing works
Unique interface and dynamics of the complex of HSP90 with a specialized cochaperone AIPL1
Srivastava, D., Yadav, R. P., Singh, S., Boyd, K. K., & Artemyev, N. O. (2023) · Structure · doi:10.1016/j.str.2022.12.014 · Cited by 14 · see citing works
Tumova, S., Doležel, D., & Jindra, M. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168332 · Cited by 14 · see citing works
Riddick, D. S. (2023) · Drug Metabolism and Disposition · doi:10.1124/dmd.122.001009 · Cited by 14 · see citing works
Liu, Y., Fang, S., Lin, T., Chen, W., Chen, Y., Wang, Y., Xiao, X., Zheng, H., Liu, L., Zhou, J., et al. (2024) · Environment International · doi:10.1016/j.envint.2024.108829 · Cited by 13 · see citing works
Zhang, S., Tang, S., Liu, Y., Xue, B., Xie, Q., Zhao, L., & Yuan, H. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1500336 · Cited by 13 · see citing works
“IS binds to the ligand-binding domain of AhR in endothelial cells and vascular smooth muscle cells, activating AhR and inducing tissue factor transcription (63, 64).”
Induction of AHR Signaling in Response to the Indolimine Class of Microbial Stress Metabolites
Patel, D., Murray, I. A., Dong, F., Annalora, A. J., Gowda, K., Coslo, D. M., Krzeminski, J., Koo, I., Hao, F., Amin, S., et al. (2023) · Metabolites · doi:10.3390/metabo13090985 · Cited by 13 · see citing works
“All three indolimine analogs (200, 214, and 248) can bind to the PAS B domain in the nanomolar affinity range, in the same primary-ligand-binding pocket of the human AHR, as defined by the high-affinity AHR ligand indirubin in the cryo-EM structure [23].”
BackgroundMethodAryl Hydrocarbon Receptor as an Anticancer Target: An Overview of Ten Years Odyssey
Hanieh, H., Bani-Ismail, M., Alfwuaires, M. A., Ibrahim, H. I., & Farhan, M. (2023) · Molecules · doi:10.3390/molecules28103978 · Cited by 11 · see citing works
“Furthermore, they have presented a structure of a complex including chaperone Hsp90 and the co-chaperone XAP2 (AhR-associated protein 9; ARA9) and indirubin-bound AhR [46].”
BackgroundInfluentialTCDD-Induced Allosteric Perturbation of the AhR:ARNT Binding to DNA
Motta, S., & Bonati, L. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119339 · Cited by 12 · see citing works
“85 Å cryo-electron microscopy (Cryo-EM) structure of the human cytosolic complex comprising the chaperone Hsp90 and the co-chaperone XAP2 proteins, along with an AhR portion including the PASB bound to the endogenous indirubin ligand, a fragment of the AhR PASB-PASA linker, and a carboxy-terminal extension of the PASB…”
BackgroundMosa, F. E. S., Alqahtani, M. A., El‐Ghiaty, M. A., Barakat, K., & El‐Kadi, A. O. S. (2024) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2024.109958 · Cited by 13 · see citing works
A mechanism for ligand-dependent activation of AHR
Guesdon, A., & Bourguet, W. (2025) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2025.02.007 · Cited by 11 · see citing works
Self-citationPerdew, G. H., Esser, C., Snyder, M., Sherr, D. H., van den Bogaard, E. H. J., McGovern, K., Fernández‐Salguero, P. M., Coumoul, X., & Patterson, A. D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065550 · Cited by 11 · see citing works
“The cryo-EM structure was accomplished by co-expression of the N-terminal half of the human AHR, HSP90/molybdate, and XAP2, with indirubin in the ligand-binding pocket [4].”
MethodUnique and Common Agonists Activate the Insect Juvenile Hormone Receptor and the Human AHR
Sedlak, D., Tuma, R., Kolla, J. N., Mokhamatam, R. B., Bahrova, L., Lisova, M., Bittova, L., & Jindra, M. (2025) · Journal of Molecular Biology · doi:10.1016/j.jmb.2024.168883 · Cited by 10 · see citing works
Emerging approaches for antagonizing the aryl hydrocarbon receptor
Dvořák, Z., Mani, S., & Vondráček, J. (2025) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2025.05.003 · Cited by 11 · see citing works
Identification of aryl hydrocarbon receptor allosteric antagonists from clinically approved drugs
Mosa, F. E. S., Alqahtani, M. A., El‐Ghiaty, M. A., Dyck, J. R. B., Barakat, K., & El‐Kadi, A. O. S. (2024) · Drug Development Research · doi:10.1002/ddr.22232 · Cited by 9 · see citing works
“…significant 0.5 fold decrease in the signal compared with the B[a]P group as Figure 10a. encompassing the repurposing of clinically approved drugs such as omeprazole and luliconazole, and the screening of chemical libraries (Giani Tagliabue et al., 2019; Gruszczyk et al., 2022; Mosa et al., 2024).”
InfluentialHaarmann‐Stemmann, T., Reichert, D., Coumoul, X., Lawrence, B. P., Perdew, G. H., Sherr, D. H., Weighardt, H., Rolfes, K. M., & Esser, C. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.116808 · Cited by 9 · see citing works
Haupt, J., Keminer, O., Neser, C., Windshügel, B., Wiltzsch, V., Schmidt, J. R., Pliushcheuskaya, P., Künze, G., Scholz, U., Müller, C., et al. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117066 · Cited by 11 · see citing works
Narita, Y., Tamura, A., Hatakeyama, S., Uemura, S., Miura, A., Haga, A., Tsuji, N., Fujie, N., Izumi, Y., Sugawara, T., et al. (2024) · FEBS Letters · doi:10.1002/1873-3468.14871 · Cited by 9 · see citing works
“The structure of the AhR-molecular chaperone complex has recently been reported from two groups using cryo-electron microscopy [29,30].”
BackgroundMethodInfluentialKimura, E. (2025) · Toxics · doi:10.3390/toxics13070596 · Cited by 8 · see citing works
“As mentioned in the introduction, AHR is localized in the cytoplasm, forming a complex with heat shock protein 90, AHR-interacting protein (also known as XAP), and p23 in the absence of its ligand [105].”
Jindra, M., & Noriega, F. G. (2025) · Elsevier eBooks · doi:10.1016/b978-0-323-95424-2.00036-4 · Cited by 7 · see citing works
Kazzaz, S. A., Shaikh, K. A., White, J., Zhou, Q., Powell, W. H., & Harhaj, E. W. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105525 · Cited by 8 · see citing works
“Similar to those of AhR, the functional roles of AIP have greatly expanded beyond AhR regulation and the xenobiotic response.”
BackgroundInfluentialBock, K. W. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115658 · Cited by 7 · see citing works
Identification of small-molecule ligand-binding sites on and in the ARNT PAS-B domain
Xu, X., Closson, J. D., Marcelino, L. P., Favaro, D. C., Silvestrini, M., Solazzo, R., Chong, L. T., & Gardner, K. H. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107606 · Cited by 7 · see citing works
“ARNT is a basic helix – loop – helix/Per-ARNT-Sim (bHLH-PAS) transcription factor, so named for its N-terminal DNA-binding bHLH motif and two PAS domains (PAS-A and PAS-B), which all mediate binding the requisite DNA and protein components required for function (7).”
Cell Signaling by Tryptophan Catabolism
Torrelli-Diljohn, A., Kulkarni, B., & Vitturi, D. A. (2026) · Biochemistry · doi:10.1021/acs.biochem.6c00179 · Cited by 7 · see citing works
Dimerization Rules of Mammalian PAS Proteins
Rojas, B. L., Vazquez-Rivera, E., Partch, C. L., & Bradfield, C. A. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168406 · Cited by 7 · see citing works
Familial isolated pituitary adenoma is independent of Ahr genotype in a novel mouse model of disease
Shen, A. L., Moran, S. M., Glover, E. A., Lin, B. C., Carney, P. R., & Bradfield, C. A. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e28231 · Cited by 6 · see citing works
Sharma, G., Abdullah, K. M., Qais, F. A., Κhan, P., Cox, J. L., Sarwar, T., Nasser, M. W., Batra, S. K., & Siddiqui, J. A. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.136921 · Cited by 6 · see citing works
A Multicomponent Reaction-Based Platform Opens New Avenues in Aryl Hydrocarbon Receptor Modulation
Rodríguez, P. N., Hartung, F., Pedrola, M., Coomar, S., Diaz-Moreno, A., Hätälä, A. M., Rolfes, K. M., Sánchez‐Vera, I., Gil, J., Molins, E., et al. (2025) · ACS Central Science · doi:10.1021/acscentsci.5c00194 · Cited by 5 · see citing works
New Insights into Hsp90 Structural Plasticity Revealed by cryoEM
Minari, K., Serrão, V. H. B., & Borges, J. C. (2024) · BioChem · doi:10.3390/biochem4020004 · Cited by 6 · see citing works
“…Å resolution of the human indirubin-bound aryl hydrocarbon receptor (AHR) complex with the chaperone Hsp90 and the cochaperone XAP2 has been elucidated, revealing a closed conformation of the Hsp90 dimer, with AHR threaded through its lumen and XAP2 providing additional support (Figure 4H) [87].”
BackgroundJonić, N., Koprivica, I., Chatzigiannis, C. M., Tsiailanis, A. D., Kyrkou, S. G., Tzakos, E. P., Pavić, A., Dimitrijević, M., Jovanović, A., Jovanović, M. B., et al. (2024) · Molecules · doi:10.3390/molecules29132988 · Cited by 6 · see citing works
Computational discovery of novel aryl hydrocarbon receptor modulators for psoriasis therapy
Santini, G., Bonati, L., & Motta, S. (2025) · Scientific Reports · doi:10.1038/s41598-025-03626-z · Cited by 6 · see citing works
Singh, S., Srivastava, D., Boyd, K. K., & Artemyev, N. O. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105576 · Cited by 6 · see citing works
“Moreover, the AIP(XAP2)-dependent HSP90 client AhR is fraction number c G M P h y d r o l ys i s ( k c p m ) threaded through the HSP90 lumen as a monomeric protein prior to its heterodimerization with ARNT (14, 15).”
BackgroundMosa, F. E. S., AlRawashdeh, S., El‐Kadi, A. O. S., & Barakat, K. (2024) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.4c00169 · Cited by 8 · see citing works
Modulation of aryl hydrocarbon receptor activity by halogenated indoles
Vrzalová, A., Vrzal, R., Nádvorník, P., Šebela, M., & Dvořák, Z. (2024) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2024.117964 · Cited by 5 · see citing works
Mosa, F. E. S., Alqahtani, M. A., El‐Ghiaty, M. A., El-Mahrouk, S. R., Barakat, K., & El‐Kadi, A. O. S. (2024) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2024.110088 · Cited by 5 · see citing works
Tian, H., Wang, L., Hardy, R., Kozhaya, L., Placek, L., Fleming, E. S., Oh, J., Unutmaz, D., & Yao, X. (2024) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.3c00386 · Cited by 4 · see citing works
Advances in understanding aryl hydrocarbon receptor structure, function, and modulation
Shang, Q., Khorasanizadeh, S., Diao, X., Rastinejad, F., & Wu, D. (2026) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2026.02.018 · Cited by 4 · see citing works
Wojtylo, P., Łapińska, N., Bellagamba, L., Camaioni, E., Mendyk, A., & Giovagnoli, S. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16111456 · Cited by 4 · see citing works
“The AhR is freed from the complex as a result of ligand binding and migrates into the nucleus where it binds to the AhR nuclear transport (ARNT) protein, thereby promoting the modulation of cellular homeostasis and the immune system [2].”
Wang, Y., Song, J., He, J., Zhang, X., Lv, Z., Dong, F., & Deng, J. (2024) · Toxicology Letters · doi:10.1016/j.toxlet.2024.02.003 · Cited by 4 · see citing works
Discovery and optimisation of pyrazolo[1,5- a ]pyrimidines as aryl hydrocarbon receptor antagonists
Bobrovs, R., Terentjeva, S., Olafsen, N. E., Dambrauskas, Ž., Gulbinas, A., Maimets, T., Teino, I., Jirgensons, A., Matthews, J. B., & Jaudzems, K. (2024) · RSC Medicinal Chemistry · doi:10.1039/d4md00266k · Cited by 4 · see citing works
Colacci, A., Corsini, E., & Jacobs, M. N. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26136310 · Cited by 4 · see citing works
“Ligand binding induces conformational changes in the AhR ligand-binding domain (LBD), including π – π stacking interactions that stabilise the receptor–ligand complex [64,65].”
Gong, X., Tan, S., Wang, L., Tian, Y., Zhang, Q., Tong, H. H. Y., Yao, X., & Liu, H. (2025) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5c00054 · Cited by 4 · see citing works
A snapshot of the aryl hydrocarbon receptor complex
Pal, M. (2023) · Structure · doi:10.1016/j.str.2023.02.007 · Cited by 4 · see citing works
The modern human aryl hydrocarbon receptor is more active when ancestralized by genome editing
Helmbrecht, N., Lackner, M., Maričić, T., & Pääbo, S. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2402159121 · Cited by 5 · see citing works
“This is compatible with a recent cryoelectronmicroscopic study of the structure of human AHR, which suggests that the valine residue at position 381 is contacting indirubin (26).”
BackgroundToward indole postbiotics precision therapy via AI-powered drug delivery technologies
Puccetti, M., Pariano, M., Anna, W. P., Maurizio, R., & Giovagnoli, S. (2025) · Current Opinion in Immunology · doi:10.1016/j.coi.2025.102692 · Cited by 4 · see citing works
Dvořák, Z., & Přikryl, J. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1823615 · Cited by 3 · see citing works
Structural basis for chaperone-guided assembly of RNA-induced silencing complex
Lee, Y.-Y., Jeong, M., Lee, H., Lee, D., Lee, J., Park, J., Kim, V. N., & Roh, S. (2026) · Nature · doi:10.1038/s41586-026-10640-2 · Cited by 3 · see citing works
“Cryo-EM structures of HSP90β–p23–AGO2, HSP90α–p23–GR (PDB: 7KRJ) 12 , and HSP90β–XAP2–AHR (PDB: 7ZUB) 24 reveal distinct client-engagement modes.”
InfluentialChoi, J., Song, W.-S., Koh, D.-H., & Kim, E. (2024) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2024.116262 · Cited by 3 · see citing works
Veroni, C., Olla, S., Brignone, M. S., Siguri, C., Formato, A., Marra, M., Manzoli, R., Macario, M. C., Ambrosini, E., Moro, E., et al. (2024) · Biomolecules · doi:10.3390/biom14040443 · Cited by 4 · see citing works
Kaleniuk, E., Holota, S. M., Skóra, B., Khyluk, D., Tabęcka-Łonczyńska, A., Lesyk, R., & Szychowski, K. A. (2024) · Applied Sciences · doi:10.3390/app14177692 · Cited by 3 · see citing works
Wang, Y., Song, J., Lin, Q., Lv, Z., Dong, F., & Jianjun, D. (2024) · Molecular & Cellular Toxicology · doi:10.1007/s13273-024-00490-2 · Cited by 3 · see citing works
Binding of ligands to the aryl hydrocarbon receptor: An overview of methods
Hrubý, J., & Dvořák, Z. (2025) · Toxicology Letters · doi:10.1016/j.toxlet.2025.01.003 · Cited by 3 · see citing works
Won, K., Jin, P.-R., Davis, L., Orjala, J., Armstrong, A. T., Wang, W. H., Kothandaraman, H., Utturkar, S. M., Bae, D., Jeong, B., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.25.678601 · Cited by 3 · see citing works
Sahoo, M. P., Samanta, L., & Satpathy, R. (2025) · Discover Chemistry. · doi:10.1007/s44371-025-00221-z · Cited by 2 · see citing works
Varlı, M., Ahn, E., Bhosle, S. R., Moon, K., Ha, H., & Kim, H. (2025) · Molecular Biomedicine · doi:10.1186/s43556-025-00309-z · Cited by 2 · see citing works
“…protein (AIP) and p23, becomes activated upon ligand binding (e.g., kynurenine), translocates to the nucleus, and induces the expression of immunosuppressive genes, including those regulatory T cells and interleukins, while also upregulating immune checkpoints such as PD-1 and PD-L1 [12– 15].”
Mammalian AHR2 loss: Evolutionary patterns, mechanisms, and relevance of biological factors
Song, W.-S., Koh, D.-H., Kim, D. H., Nomiyama, K., Iwata, H., & Kim, E.-Y. (2026) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2026.119899 · Cited by 2 · see citing works
Koellisch, K., Blattner, C., Motta, S., Wesslowski, J., Rothley, M., Büchel, S., Sirounian, S., Segatto, I., Weber, H. T., Müller, J., et al. (2026) · iScience · doi:10.1016/j.isci.2026.115936 · Cited by 2 · see citing works
“29 The reporter HELN hER α cell line was obtained by transfecting human HeLa cells with the ERE-responsive gene ERE-β Globin-luciferase-Luc-neomycin and the pSG5-hER α -puromycin plasmids as previously described.”
Self-citationde la Lastra, J. M. P., Andrés, C. M. C., Munguira, E. B., Juan, C. A., & Lebeña, E. P. (2026) · Current Issues in Molecular Biology · doi:10.3390/cimb48050529 · Cited by 2 · see citing works
“AhR is thus a context-dependent integrator whose output is tuned by transporter delivery, local deconjugation/oxidation, and individual metabotype, most evident at barrier and tumour-adjacent sites during late, microbiome-dominated windows (engagement methodology: Section 5) [80].”
The CLOCK–BMAL1 complex in circadian regulation: structure, mechanisms, and therapeutic targeting
Kamel, E. M., Khadrawy, S. M., Allam, A. A., Ahmed, N. A., Alkhayl, F. F. A., & Lamsabhi, A. M. (2026) · Inflammation Research · doi:10.1007/s00011-026-02275-w · Cited by 2 · see citing works
“For CLOCK–BMAL1 design, the AhR precedent argues that PAS-B ligands may also rewire cofactor/chromatin partner interactions or subcellular trafficking without breaking the heterodimer, aligning with the “tuning” rather than “off-switch” paradigm [61].”
Abduh, M., Alwassil, O., Aldaqal, S. M., Alfwuaires, M. A., Farhan, M., & Hanieh, H. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116079 · Cited by 2 · see citing works
Zhang, T., He, C. J., Ota, S., Kitakaze, T., Yamaji, R., Shimazu, S., Yamashita, Y., & Ashida, H. (2024) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202400185 · Cited by 2 · see citing works
2,3,7,8-tetrachlorodibenzofuran modulates intestinal microbiota and tryptophan metabolism in mice
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Methylcarvones as immunomodulators through antagonism of aryl hydrocarbon receptor
Zůvalová, I., Grycová, A., Hrubý, J., Illéš, P., Soural, M., Kováč, O., Šebela, M., Petr Bachleda, A., Kriegová, E., Trajerová, M., et al. (2025) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2025.109256 · Cited by 1 · see citing works
Ruano, L., Pérez‐Barcia, Á., Palmisano, V. F., Nogueira, J. J., Mandado, M., & Ramos‐Berdullas, N. (2026) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.5c02555 · Cited by 1 · see citing works
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Beyond a Passive Tether: Structural Insights into the Disordered Tail of Hsp90
Edinach, E., Giannouli, A., Dalaloyan, A., Oranges, M., Banik, D., Yardeni, E., Elimelech, A., Sattler, M., Ntermanakis, E., Su, X.-C., et al. (2026) · Journal of the American Chemical Society · doi:10.1021/jacs.6c04189 · Cited by 1 · see citing works
- Authors
- Gruszczyk, J., Grandvuillemin, L., Lai-Kee-Him, J., Paloni, M., Savva, C. G., Germain, P., Grimaldi, M., Boulahtouf, A., Kwong, H.-S., Bous, J., Ancelin, A., Bechara, C., Barducci, A., Balaguer, P., & Bourguet, W.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- University of Leicester (GB)
- Inserm (FR)
- Karolinska Institutet (SE)
- Corresponding author
- Gruszczyk, Jakub
- Bourguet, William
- ORCID
- Venue
- Nature Communications
- Published
- 2022-11-16
- Volume
- 13
- Issue
- 1
- Pages
- 7010-7010
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC9668932
- OpenAlex
- W4309473730
- Cited by
- 137
- References
- 58
- Citations by year
- 2026: 38 · 2025: 28 · 2024: 39 · 2023: 31 · 2022: 1
- FWCI
- 8.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- HAL (submittedVersion, cc-by-sa)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- European Commission (825489, HORIZON2020)
- Agence Nationale de la Recherche (ANR-16-IDEX-0006, ANR‐16‐IDEX‐, ANR-10-INBS-04-01, 10-INBS-04, 10-INBS-04-01, ANR‐10_INBS‐04, ANR-16, INBS-04-01, ANR-10, ANR-10-LABX-0012, ANR-10-INBS-0004)
- Université de Montpellier (ANR_16-IDEX-0 0 06)
- French Infrastructure for Integrated Structural Biology (ANR-10-INBS, ANR-10-INBS-04)
- Région Occitanie Pyrénées-Méditerranée
- Laboratoire d'Excellence EpiGenMed
- Medical Research Council (MC_PC_17136, ANR-10-INBS-04)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- aryl hydrocarbon receptor, HSP90, indirubin, ligand binding, PAS-B domain, ligand specificity, receptor activation, transcription factors, structure-based drug design
- MeSH terms
- Cytosol, Humans, Ligands, Receptors, Aryl Hydrocarbon, HSP90 Heat-Shock Proteins, Cryoelectron Microscopy, Intracellular Signaling Peptides and Proteins, Basic Helix-Loop-Helix Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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