Structural basis of glucocorticoid receptor signaling bias.
allostery
biased signaling
cooperativity
drug discovery
nuclear receptors
Journal
Journal of neuroendocrinology
ISSN: 1365-2826
Titre abrégé: J Neuroendocrinol
Pays: United States
ID NLM: 8913461
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
revised:
15
09
2022
received:
21
05
2022
accepted:
23
09
2022
medline:
29
3
2023
pubmed:
13
10
2022
entrez:
12
10
2022
Statut:
ppublish
Résumé
Dissociation between the healthy and toxic effects of cortisol, a major stress-responding hormone has been a widely used strategy to develop anti-inflammatory glucocorticoids with fewer side effects. Such strategy falls short when treating brain disorders as timing and activity state within large-scale neuronal networks determine the physiological and behavioral specificity of cortisol response. Advances in structural molecular dynamics posit the bases for engineering glucocorticoids with precision bias for select downstream signaling pathways. Design of allosteric and/or cooperative control for the glucocorticoid receptor could help promote the beneficial and reduce the deleterious effects of cortisol on brain and behavior in disease conditions.
Substances chimiques
Glucocorticoids
0
Receptors, Glucocorticoid
0
Hydrocortisone
WI4X0X7BPJ
Anti-Inflammatory Agents
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13203Informations de copyright
© 2022 British Society for Neuroendocrinology.
Références
Garabedian MJ, Harris CA, Jeanneteau F. Glucocorticoid receptor action in metabolic and neuronal function. F1000Res. 2017;6:1208.
Arango-Lievano M, Lambert WM, Jeanneteau F. Molecular biology of glucocorticoid signaling. Adv Exp Med Biol. 2015;872:33-57.
Groeneweg FL, Karst H, de Kloet ER, Joels M. Rapid non-genomic effects of corticosteroids and their role in the central stress response. J Endocrinol. 2011;209(2):153-167.
Liston C, Cichon JM, Jeanneteau F, J. Z, Chao MV, Gan WB. Circadian glucocorticoid oscillations promote learning-dependent synapse formation and maintenance. Nat Neurosci 2013; 16(6): 698-705.
Hu W, Zhang M, Czéh B, Flügge G, Zhang W. Stress impairs GABAergic network function in the hippocampus by activating nongenomic glucocorticoid receptors and affecting the integrity of the parvalbumin-expressing neuronal network. Neuropsychopharmacology. 2010;35(8):1693-1707.
Di S, Maxson MM, Franco A, Tasker JG. Glucocorticoids regulate glutamate and GABA synapse-specific retrograde transmission via divergent nongenomic signaling pathways. J Neurosci. 2009;29(2):393-401.
Karst H, Berger S, Turiault M, Tronche F, Schutz G, Joels M. Mineralocorticoid receptors are indispensable for nongenomic modulation of hippocampal glutamate transmission by corticosterone. Proc Natl Acad Sci U S A. 2005;102(52):19204-19207.
Karst H, den Boon FS, Vervoort N, Adrian M, Kapitein LC, Joëls M. Non-genomic steroid signaling through the mineralocorticoid receptor: involvement of a membrane-associated receptor? Mol Cell Endocrinol. 2022;541:111501.
Sevilla LM, Jiménez-Panizo A, Alegre-Martí A, Estébanez-Perpiñá E, Caelles C, Pérez P. Glucocorticoid resistance: interference between the glucocorticoid receptor and the MAPK Signalling pathways. Int J Mol Sci. 2021;22(18):10049.
Clark AR, Belvisi MG. Maps and legends: the quest for dissociated ligands of the glucocorticoid receptor. Pharmacol Ther. 2012;134(1):54-67.
Savas M, Vinkers CH, Rosmalen JGM, et al. Systemic and local corticosteroid use is associated with reduced executive cognition, and mood and anxiety disorders. Neuroendocrinology. 2020;110(3-4):282-291.
van der Meulen M, Amaya JM, Dekkers OM, Meijer OC. Association between use of systemic and inhaled glucocorticoids and changes in brain volume and white matter microstructure: a cross-sectional study using data from the UK biobank. BMJ Open. 2022;12(8):e062446.
Bledsoe RK, Montana VG, Stanley TB, et al. Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell. 2002;110(1):93-105.
Weikum ER, Okafor CD, D′Agostino EH, Colucci JK, Ortlund EA. Structural analysis of the glucocorticoid ReceptorLigand-binding domain in complex with TriamcinoloneAcetonide and a fragment of the atypical Coregulator, SmallHeterodimer partner. Mol Pharmacol. 2017;92:12-21.
Weikum ER, Knuesel MT, Ortlund EA, Yamamoto KR. Glucocorticoid receptor control of transcription: precision and plasticity via allostery. Nat Rev Mol Cell Biol. 2017;18(3):159-174.
Kenakin T. Theoretical aspects of GPCR-ligand complex pharmacology. Chem Rev. 2017;117(1):4-20.
Shiau AK, Barstad D, Loria PM, et al. The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell. 1998;95(7):927-937.
Baker ME, Chandsawangbhuwana C, Ollikainen N. Structural analysis of the evolution of steroid specificity in the mineralocorticoid and glucocorticoid receptors. BMC Evol Biol. 2007;7:24.
Edman K, Hosseini A, Bjursell MK, et al. Ligand binding mechanism in steroid receptors: from conserved plasticity to differential evolutionary constraints. Structure. 2015;23(12):2280-2290.
Schoch GA, D′Arcy B, Stihle M, et al. Molecular switch in the glucocorticoid receptor: active and passive antagonist conformations. J Mol Biol. 2010;395(3):568-577.
Hu X, Du S, Tunca C, et al. The antagonists but not partial agonists of glucocorticoid receptor ligands show substantial side effect dissociation. Endocrinology. 2011;152(8):3123-3134.
Kroon J, Viho EMG, Gentenaar M, et al. The development of novel glucocorticoid receptor antagonists: from rational chemical design to therapeutic efficacy in metabolic disease models. Pharmacol Res. 2021;168:105588.
McMahon SK, Pretorius CJ, Ungerer JP, et al. Neonatal complete generalized glucocorticoid resistance and growth hormone deficiency caused by a novel homozygous mutation in helix 12 of the ligand binding domain of the glucocorticoid receptor gene (NR3C1). J Clin Endocrinol Metab. 2010;95(1):297-302.
Nicolaides NC, Galata Z, Kino T, Chrousos GP, Charmandari E. The human glucocorticoid receptor: molecular basis of biologic function. Steroids. 2010;75(1):1-12.
Köhler C, Carlström G, Gunnarsson A, et al. Dynamic allosteric communication pathway directing differential activation of the glucocorticoid receptor. Sci Adv. 2020;6(29):eabb5277.
Hu X, Pang J, Zhang J, et al. Discovery of novel GR ligands toward Druggable GR antagonist conformations identified by MD simulations and Markov state model analysis. Adv Sci (Weinh). 2022;9(3):e2102435.
Vandevyver S, Dejager L, Tuckermann J, Libert C. New insights into the anti-inflammatory mechanisms of glucocorticoids: an emerging role for glucocorticoid-receptor-mediated transactivation. Endocrinology. 2013;154(3):993-1007.
De Bosscher K, Beck IM, Ratman D, Berghe WV, Libert C. Activation of the glucocorticoid receptor in acute inflammation: the SEDIGRAM concept. Trends Pharmacol Sci. 2016;37(1):4-16.
De Bosscher K, Desmet SJ, Clarisse D, Estébanez-Perpiña E, Brunsveld L. Nuclear receptor crosstalk-defining the mechanisms for therapeutic innovation. Nat Rev Endocrinol. 2020;16(7):363-377.
Zalachoras I, Houtman R, Atucha E, et al. Differential targeting of brain stress circuits with a selective glucocorticoid receptor modulator. Proc Natl Acad Sci U S A. 2013;110(19):7910-7915.
Ricketson D, Hostick U, Fang L, Yamamoto KR, Darimont BD. A conformational switch in the ligand-binding domain regulates the dependence of the glucocorticoid receptor on Hsp90. J Mol Biol. 2007;368(3):729-741.
Munier CC, De Maria L, Edman K, et al. Glucocorticoid receptor Thr524 phosphorylation by MINK1 induces interactions with 14-3-3 protein regulators. J Biol Chem. 2021;296:100551.
Motlagh HN, Hilser VJ. Agonism/antagonism switching in allosteric ensembles. Proc Natl Acad Sci U S A. 2012;109(11):4134-4139.
Meijer FA, Leijten-van de Gevel IA, de Vries RMJM, Brunsveld L. Allosteric small molecule modulators of nuclear receptors. Mol Cell Endocrinol. 2019;485:20-34.
Li J, White JT, Saavedra H, et al. Genetically tunable frustration controls allostery in an intrinsically disordered transcription factor. elife. 2017;6:e30688.
White JT, Rives J, Tharp ME, Wrabl JO, Thompson EB, Hilser VJ. Tumor susceptibility gene 101 regulates the glucocorticoid receptor through disorder-mediated Allostery. Biochemistry. 2021;61(21):1647-1657.
Kumar R, Volk DE, Li J, Lee JC, Gorenstein DG, Thompson EB. TATA box binding protein induces structure in the recombinant glucocorticoid receptor AF1 domain. Proc Natl Acad Sci U S A. 2004;101(47):16425-16430.
Liberman AC, Antunica-Noguerol M, Arzt E. Modulation of the glucocorticoid receptor activity by post-translational modifications. Nucl Rec Res. 2014;1:1-15.
Garza AM, Khan SH, Kumar R. Site-specific phosphorylation induces functionally active conformation in the intrinsically disordered N-terminal activation function (AF1) domain of the glucocorticoid receptor. Mol Cell Biol. 2010;30(1):220-230.
Khan SH, McLaughlin WA, Kumar R. Site-specific phosphorylation regulates the structure and function of an intrinsically disordered domain of the glucocorticoid receptor. Sci Rep. 2017;7(1):15440.
Kumar R, Thompson EB. Role of phosphorylation in the modulation of the glucocorticoid Receptor′s intrinsically disordered domain. Biomolecules. 2019;9(3):95.
Lu NZ, Cidlowski JA. Translational regulatory mechanisms generate N-terminal glucocorticoid receptor isoforms with unique transcriptional target genes. Mol Cell. 2005;18(3):331-342.
Oakley RH, Ramamoorthy S, Foley JF, Busada JT, Lu NZ, Cidlowski JA. Glucocorticoid receptor isoform-specific regulation of development, circadian rhythm, and inflammation in mice. FASEB J. 2018;32(10):5258-5271.
Cao Y, Bender IK, Konstantinidis AK, et al. Glucocorticoid receptor translational isoforms underlie maturational stage-specific glucocorticoid sensitivities of dendritic cells in mice and humans. Blood. 2013;121(9):1553-1562.
Paugh SW, Bonten EJ, Savic D, et al. NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells. Nat Genet. 2015;47(6):607-614.
Galliher-Beckley AJ, Williams JG, Cidlowski JA. Ligand-independent phosphorylation of the glucocorticoid receptor integrates cellular stress pathways with nuclear receptor signaling. Mol Cell Biol. 2011;31(23):4663-4675.
Jumper J, Evans R, Pritzel A, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021;596(7873):583-589.
Varadi M, Anyango S, Deshpande M, et al. AlphaFold protein structure database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Res. 2021;50(D1):D439-D444.
de Vink PJ, Koops AA, D′Arrigo G, Cruciani G, Spyrakis F, Brunsveld L. Cooperativity as quantification and optimization paradigm for nuclear receptor modulators. Chem Sci. 2022;13(9):2744-2752.
Hilser VJ, Thompson EB. Structural dynamics, intrinsic disorder, and allostery in nuclear receptors as transcription factors. J Biol Chem. 2011;286(46):39675-39682.
Johnson TA, Paakinaho V, Kim S, Hager GL, Presman DM. Genome-wide binding potential and regulatory activity of the glucocorticoid receptor's monomeric and dimeric forms. Nat Commun. 2021;12(1):1987.
Hudson WH, Youn C, Ortlund EA. The structural basis of direct glucocorticoid-mediated transrepression. Nat Struct Mol Biol. 2013;20(1):53-58.
Newton R, Holden NS. Separating transrepression and transactivation: a distressing divorce for the glucocorticoid receptor? Mol Pharmacol. 2007;72(4):799-809.
Hudson WH, Vera IMS, Nwachukwu JC, et al. Cryptic glucocorticoid receptor-binding sites pervade genomic NF-κB response elements. Nat Commun. 2018;9(1):1337.
Vanderhaeghen T, Timmermans S, Watts D, et al. Reprogramming of glucocorticoid receptor function by hypoxia. EMBO Rep. 2022;23(1):e53083.
Keenan CR, Lew MJ, Stewart AG. Biased signalling from the glucocorticoid receptor: renewed opportunity for tailoring glucocorticoid activity. Biochem Pharmacol. 2016;112:6-12.
Wang Z, Frederick J, Garabedian MJ. Deciphering the phosphorylation “code” of the glucocorticoid receptor in vivo. J Biol Chem. 2002;277(29):26573-26580.
Gardner KH, Montminy M. Can you hear me now? Regulating transcriptional activators by phosphorylation. Sci Signal. 2005;301:pe44.
Arango-Lievano M, Lambert WM, Bath KG, Garabedian MJ, Chao MV, Jeanneteau F. Neurotrophic-priming of glucocorticoid receptor signaling is essential for neuronal plasticity to stress and antidepressant treatment. Proc Natl Acad Sci U S A. 2015;112(51):15737-15742.
Lambert WM, Xu C-F, Neubert TA, Chao MV, Garabedian MJ, Jeanneteau F. BDNF-signaling rewrites the glucocorticoid transcriptome via glucocorticoid receptor phosphorylation. Mol Cell Biol. 2013;33(18):3700-3714.
Jeanneteau F, Borie A, Chao M, Garabedian M. Bridging the gap between BDNF and glucocorticoid effects on brain networks. Neuroendocrinology. 2019;109(3):277-284.
Arango-Lievano M, Jeanneteau F. Timing and crosstalk of glucocorticoid signaling with cytokines, neurotransmitters and growth factors. Pharmacol Res. 2016;113(Pt A):1-17.
Jeanneteau F, Coutellier L. The glucocorticoid footprint on the memory engram. Curr Opin Endocri Metab Res. 2022, in press. doi:10.1016/j.coemr.2022.100378
Huzard D, Rappeneau V, Meijer OC, et al. Experience and activity-dependent control of glucocorticoid receptors during the stress response in large-scale brain networks. Stress. 2020;24(2):130-153.
Biggadike K, Bledsoe RK, Coe DM, et al. Design and x-ray crystal structures of high-potency nonsteroidal glucocorticoid agonists exploiting a novel binding site on the receptor. Proc Natl Acad Sci U S A. 2009;106(43):18114-18119.
Jin Z, Lin H, Srinivasan S, et al. Synthesis of novel steroidal agonists, partial agonists, and antagonists for the glucocorticoid receptor. Bioorg Med Chem Lett. 2017;27(2):347-353.
Wang RY, Noddings CM, Kirschke E, Myasnikov AG, Johnson JL, Agard DA. Structure of Hsp90-Hsp70-hop-GR reveals the Hsp90 client-loading mechanism. Nature. 2022;601(7893):460-464.
Broekema MF, Hollman DAA, Koppen A, et al. Profiling of 3696 nuclear receptor-Coregulator interactions: a resource for biological and clinical discovery. Endocrinology. 2018;159(6):2397-2407.
Bakker E, Tian K, Mutti L, Demonacos C, Schwartz JM, Krstic-Demonacos M. Insight into glucocorticoid receptor signalling through interactome model analysis. PLoS Comput Biol. 2017;13(11):e1005825.
Kalafatakis K, Russell GM, Harmer CJ, et al. Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man. Proc Natl Acad Sci U S A. 2018;115(17):E4091-E4100.
Sarabdjitsingh RA, Spiga F, Oitzl MS, et al. Recovery from disrupted ultradian glucocorticoid rhythmicity reveals a dissociation between hormonal and behavioural stress responsiveness. J Neuroendocrinol. 2010;22(8):862-871.
Meijer OC, Koorneef LL, Kroon J. Glucocorticoid receptor modulators. Endocrinology (Paris). 2018;79(3):107-111.
Vishweshwaraiah YL, Chen J, Dokholyan NV. Engineering an allosteric control of protein function. J Phys Chem B. 2021;125(7):1806-1814.
McCormick JW, Russo MA, Thompson S, Blevins A, Reynolds KA. Structurally distributed surface sites tune allosteric regulation. elife. 2021;10:e68346.
Wang J, Jain A, McDonald LR, Gambogi C, Lee AL, Dokholyan NV. Mapping allosteric communications within individual proteins. Nat Commun. 2020;11(1):3862.
Vickerman BM, Zywot EM, Tarrant TK, Lawrence DS. Taking phototherapeutics from concept to clinical launch. Nat Rev Chem. 2021;5(11):816-834.
Gil AA, Carrasco-López C, Zhu L, et al. Optogenetic control of protein binding using light-switchable nanobodies. Nat Commun. 2020;11(1):4044.
Paoletti P, Ellis-Davies GCR, Mourot A. Optical control of neuronal ion channels and receptors. Nat Rev Neurosci. 2019;20(9):514-532.
Morstein J, Trads JB, Hinnah K, et al. Optical control of the nuclear bile acid receptor FXR with a photohormone. Chem Sci. 2019;11(2):429-434.
Hinnah K, Willems S, Morstein J, et al. Photohormones enable optical control of the peroxisome proliferator-activated receptor γ (PPARγ). J Med Chem. 2020;63(19):10908-10920.
Barnes PJ, Adcock IM. Glucocorticoid resistance in inflammatory diseases. Lancet. 2009;373(9678):1905-1917.
Bouazza B, Debba-Pavard M, Amrani Y, et al. Basal p38 mitogen-activated protein kinase regulates unliganded glucocorticoid receptor function in airway smooth muscle cells. Am J Respir Cell Mol Biol. 2014;50(2):301-315.
Hoppstädter J, Ammit AJ. Role of dual-specificity phosphatase 1 in glucocorticoid-driven anti-inflammatory responses. Front Immunol. 2019;10:1446.
Arango-Lievano M, Peguet C, Catteau M, et al. Deletion of Neurotrophin signaling through the glucocorticoid receptor pathway causes tau neuropathology. Sci Rep. 2016;6:37231.
De Bosscher K, Vanden Berghe W, Beck IM, et al. A fully dissociated compound of plant origin for inflammatory gene repression. Proc Natl Acad Sci U S A. 2005;102(44):15827-15832.
Van Moortel L, Thommis J, Maertens B, et al. Novel assays monitoring direct glucocorticoid receptor protein activity exhibit high predictive power for ligand activity on endogenous gene targets. Biomed Pharmacother. 2022;152:113218.