Steroid-hormone rapid actions, membrane receptors and a conformational ensemble model
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Norman, A. W. & Litwack, G. L. Hormones (Academic, San Diego, 1997).
Krausz, C. et al. Intracellular calcium increase and acrosome reaction if response to progesterone in human spermatozoa are correlated with in vitro fertilization. Human Reprod. 10, 120–124 (1995).
Meizel, S., Turner, K. O. & Nuccitelli, R. Progesterone triggers a wave of increased free calcium during the human sperm acrosome reaction. Dev. Biol. 182, 67–75 (1997).
Schwartz, Z. et al. 1α, 25(OH)2D3 regulates chondrocyte matrix vesicle protein kinase C (PKC) directly via G-protein-dependent mechanisms and indirectly via incorporation of PKC during matrix vesicle biogenesis. J. Biol. Chem. 277, 11828–11837 (2002).
Selye, H. Correlations between the chemical structure and the pharmacological actions of the steroids. Endocrinology 30, 437–453 (1942). In the rapid response arena, there were a series of papers from the Selye laboratory in the late 1930s describing a correlation between the chemical structures of steroids and their rapid pharmaco-logical actions as anaesthetics, which are summarized in reference 5.
Klein, K. & Henk, K. Klinisch-experimentelle untersuchungen uber den einfluss von aldosteron auf haemodynamik and gerinnung. Z. Kreisl. Forsch. 40–53 (1964).
Spach, C. & Streeten, D. H. Retardation of sodium exchange in dog erythrocytes by physiological concentrations of aldosterone, in vitro. J. Clin. Invest. 43, 217–227 (1963). The modern era of rapid responses to steroid hormones was initiated by the results presented in reference 6, which is a demonstration of acute (5 min) in vivo cardiovascular effects of aldosterone in man, and reference 7, which describes the in vitro effects of physiological concentrations of aldosterone on Na+ exchange in erythrocytes.
Jensen, E. V., De Sombre, E. R. & Jungblut, P. W. Interaction of estrogens with receptor sites in vivo and in vitro. Proc. Sec. Int. Cong. 132, 492–500 (1966).
Toft, D. & Gorski, J. A receptor molecule for estrogens: Isolation from the rat uterus and preliminary characterization. Proc. Natl Acad. Sci. USA 55, 1574–1581 (1966). References 8 and 9 are key papers in the genomic response arena, providing the first descriptions of the existence of a receptor the oestradiol receptor for a steroid hormone.
Li, J. & Chory, J. A putative leucine-rich repeat receptor kinase involved in brassinosteroid signal transduction. Cell 90, 929–938 (1997). The first paper reporting the cloning of a novel membrane receptor for a steroid hormone (the plant brassinolide), which binds to an outer-cell-membrane receptor that is linked to a rapid response.
Walters, M. R., Hunziker, W. & Norman, A. W. A mathematical model describing the subcellular localization of non-membrane bound steroid, seco-steroid, and thyronine receptors. J. Steroid Biochem. Mol. Biol. 15, 491–495 (1981).
Hermanson, O., Glass, C. K. & Rosenfeld, M. G. Nuclear receptor coregulators: multiple modes of modification. Trends Endocrinol. Metab. 13, 55–60 (2002).
McKenna, N. J. & O'Malley, B. W. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell 108, 465–474 (2002).
Altucci, L. & Gronemeyer, H. Nuclear receptors in cell life and death. Trends Endocrinol. Metab. 12, 460–468 (2001).
Moras, D. & Gronemeyer, H. The nuclear receptor ligand-binding domain: structure and function. Curr. Opin. Cell Biol. 10, 384–391 (1998).
Weatherman, R. V., Fletterick, R. J. & Scanlon, T. S. Nuclear receptor ligands and ligand-binding domains. Annu. Rev. Biochem. 68, 559–582 (1999). A detailed but clear review of the similarities (many) and differences (few) of the first five members of the steroid receptor superfamily to have their atomic structure determined by X-ray crystallography.
Bourguet, W., Germain, P. & Gronemeyer, H. Nuclear receptor ligand-binding domains: three-dimensional structures, molecular interactions and pharmacological implications. Trends Pharmacol. Sci. 21, 381–388 (2000).
Egea, P. F., Klaholz, B. P. & Moras, D. Ligand–protein interactions in nuclear receptors of hormones. FEBS Lett. 476, 62–67 (2000).
Haussler, M. R. & Norman, A. W. Chromosomal receptor for a vitamin D metabolite. Proc. Natl Acad. Sci. USA 62, 155–162 (1969). First paper describing the existence of a nuclear receptor for the hormone form of vitamin D, namely 1α,25(OH) 2 -vitamin D 3 . Up to this time, it was not appreciated that the biological actions of vitamin D were mediated through a daughter metabolite functioning as a steroid hormone with a cognate receptor.
Bogan, A. A., Cohen, F. E. & Scanlan, T. S. Natural ligands of nuclear receptors have conserved volumes. Nature Struct. Biol. 5, 679–681 (2003). This short communication will be of interest to anyone interested in the theory of divergent evolution of the nuclear receptor superfamily.
Norman, A. W. et al. Comparison of 6s-cis and 6-s-trans locked analogs of 1α, 25(OH)2-vitamin D3 indicates that the 6-s-cis conformation is preferred for rapid nongenomic biological responses and that neither 6-s-cis nor 6-s-trans locked analogs are preferred for genomic biological responses. Mol. Endocrinol. 11, 1518–1531 (1997).
Norman, A. W. et al. Molecular tools for study of genomic and rapid signal transduction responses initiated by 1α, 25(OH)2-vitamin D3 . Steroids 67, 457–466 (2002).
Kousteni, S. et al. Reversal of bone loss in mice by nongenotropic signaling of sex steroids. Science 298, 843–846 (2002). Illustrates the importance of steroid structure in facilitating tissue-specific activities where all signalling (genomic and non-genomic) was described as being mediated through sterol occupancy of the nuclear receptor LBD. Interestingly, the structure of the oestradiol analogue oestren is more reminiscent of the structure of the androgen DHT than it is of oestradiol, because of the similar DHT and oestren A-ring chemistries.
Kousteni, S. et al. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell 104, 719–730 (2001). The precursor to reference 23, this paper demonstrates the sex non-specific anti-apoptotic effect of oestradiol and DHT on bone and other cell types, requiring only the nuclear LBD (blocked by classic anti-oestrogens and anti-androgens). Distinct genomic and non-genomic activities of both the oestrogen and androgen receptor are dissected by synthetic ligands and a model is posited in which the complex leading to a non-genomic response is formed in a rapid, but transient, association with the ligand. By contrast, the complex leading to the genomic response is posited to have a comparatively longer half-life.
Swann, S. L. et al. Structure-based design of selective agonists for a rickets-associated mutant of the vitamin D receptor. J. Am. Chem. Soc. 124, 13795–13805 (2002).
Swann, S. L., Bergh, J. J., Farach-Carson, M. C. & Koh, J. T. Rational design of vitamin D3 analogs which selectively restore activity to a vitamin D receptor mutant associated with rickets. Org. Lett. 4, 3863–3866 (2002).
Anderson, R. G. & Jacobson, K. A role for lipid shells in targeting proteins to caveolae, rafts, and other lipid domains. Science 296, 1821–1825 (2002).
Razani, B., Woodman, S. E. & Lisanti, M. P. Caveolae: from cell biology to animal physiology. Pharmacol. Rev. 54, 431–467 (2002). A comprehensive review of the biological function(s) of caveolae.
He, Z. et al. Perception of brassinosteroids by the extracellular domain of the receptor kinase BRI1. Science 288, 2360–2363 (2000).
Zhu, Y. et al. Cloning, expression, and characterization of a membrane progestin receptor and evidence it is an intermediary in meiotic maturation of fish oocytes. Proc. Natl Acad. Sci. USA 100, 2231–2236 (2003).
Zhu, Y., Bond, J. & Thomas, P. Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor. Proc. Natl Acad. Sci. USA 100, 2237–2242 (2003). References 31 and 32 report the first cloning of a non-plant-membrane receptor for a steroid hormone, progestin, linked to rapid responses. This led to discovery of a new vertebrate gene family of membrane proteins, described in reference 32.
Chambliss, K. L. et al. ERβ has nongenomic action in caveolae. Mol. Endocrinol. 16, 938–946 (2002).
Song, R. X. et al. Linkage of rapid estrogen action to MAPK activation by ERα-Shc association and Shc pathway activation. Mol. Endocrinol. 16, 116–127 (2002).
Norman, A. W., Olivera, C. J., Barreto Silva, F. R. & Bishop, J. E. A specific binding protein/receptor for 1α, 25-dihydroxy D3 is present in an intestinal caveolae membrane fraction. Biochem. Biophys. Res. Commun. 298, 414–419 (2002).
Barbato, J. C., Mulrow, P. J., Shapiro, J. I. & Franco-Saenz, R. Rapid effects of aldosterone and spironolactone in the isolated working rat heart. Hypertension 40, 130–135 (2002).
Huhtakangas, J. A., Norman, A. W., Bishop, J. E. & Olivera, C. J. 1α, 25(OH)2D3 binding by vitamin D receptor present in caveolae enriched fraction of chick and wild type mouse duodenum, lung and kidney but not comparable VDR-knockout tissues. J. Steroid Biochem. Mol. Biol. (in the press).
Li, S., Couet, J. & Lisanti, M. P. Src tyrosine kinases, Gα subunits, and H-Ras share a common membrane-anchored scaffolding protein, caveolin. J. Biol. Chem. 271, 29182–29190 (1996).
Razandi, M. et al. Identification of a structural determinant necessary for the localization and function of estrogen receptor alpha at the plasma membrane. Mol. Cell. Biol. 23, 1633–1646 (2003).
Wyckoff, M. H. et al. Plasma membrane estrogen receptors are coupled to endothelial nitric- oxide synthase through Gai . J. Biol. Chem. 276, 27071–27076 (2001).
Razandi, M., Pedram, A., Park, S. T. & Levin, E. R. Proximal events in signaling by plasma membrane estrogen receptors. J. Biol. Chem. 278, 2701–2712 (2003).
Castoria, G. et al. Androgen-stimulated DNA synthesis and cytoskeletal changes in fibroblasts by a nontranscriptional receptor action. J. Cell Biol. 161, 547–556 (2003).
Rosner, W. et al. Sex hormone-binding globulin mediates steroid hormone signal transduction at the plasma membrane. J. Steroid Biochem. Mol. Biol. 69, 481–485 (1999).
DiMartino, S. J., Shah, A. B., Trujillo, G. & Kew, R. R. Elastase controls the binding of the vitamin D-binding protein (Gc-globulin) to neutrophils: a potential role in the regulation of C5α co-chemotactic activity. J. Immunol. 166, 2688–2694 (2001).
Harvey, B. J. et al. Non-genomic convergent and divergent signalling of rapid responses to aldosterone and estradiol in mammalian colon. Steroids 67, 483–491 (2003).
Slater, S. J. et al. Direct activation of protein kinase C by 1α, 25-dihydroxyvitamin D3 . J. Biol. Chem. 270, 6639–6643 (1995).
Stubbs, C. D., Slater, S. J., Okamura, W. H. & Norman, A. W. in Vitamin D: Chemistry, Biology and Clinical Applications of the Steroid Hormone (eds Norman, A. W., Bouillon, R. & Thomasset, M) 339–346 (University of California, Riverside, Riverside, 1997).
Bourguet, W. et al. Crystal structure of the ligand-binding domain of the human nuclear receptor RXRα. Nature 375, 377–382 (1995).
Renaud, J. P. et al. Crystal structure of the RAR-γ ligand-binding domain bound to all-trans retinoic acid. Nature 378, 681–689 (1995). In addition to reference 58, references 48 and 49 represent break-through papers describing for the first time the X-ray structures of the LBDs of three members of the superfamily of steroid nuclear receptors. The exciting observation was that the overall three-dimensional structure of the LBDs for these three diverse hormones were very similar.
Willson, T. M. & Moore, J. T. Genomics verus orphan nuclear receptors: a half-time report. Mol. Endocrinol. 16, 1135–1144 (2002).
Kliewer, S. A., Lehmann, J. M. & Willson, T. M. Orphan nuclear receptors: shifting endocrinology into reverse. Science 284, 757–760 (1999).
Brzozowski, A. M. et al. Molecular basis of agonism and antagonism of the oestrogen receptor. Nature 389, 753–758 (1997).
Gibbs, P. E. M. & Dugaiczyk, A. Origin of structural domains of the serum albumin gene family and a predicted structure of the gene for vitamin D binding protein. Mol. Biol. Evol. 4, 364–379 (1987).
Mizwicki, M. T. & Norman, A. W. Two key proteins of the vitamin D endocrine system come into crystal clear focus: comparison of the X-ray structures of the nuclear receptor for 1α, 25(OH)2 vitamin D3, the plasma vitamin D binding protein, and their ligands. J. Bone Miner. Res. 18, 795–806 (2003).
Grishkovskaya, I. et al. Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain. EMBO J. 19, 504–512 (2000).
Hammond, G. L., Avvakumov, G. V. & Muller, Y. A. Structure/function analyses of human sex hormone-binding globulin: effects of zinc on steroid-binding specificity. J. Steroid Biochem. Mol. Biol. 85, 195–200 (2003).
Mizwicki, M. T., Norman, D. P. G., & Norman, A. W. Vitamin D recepetor [VDR] ligand binding: conformational ensembles explain both genomic and rapid responses. J. Steroid Biochem. Mol. Biol. (in the press).
Wagner, R. L. et al. A structural role for hormone in the thyroid hormone receptor. Nature 378, 690–697 (1995). The TR-β structure was one of the first ligand-occupied nuclear-receptor structures solved. The authors put forward a hypothesis of how ligand can enter the X-ray (genomic) pocket through the H2/β-sheet region. This hypothesis and the large amount of loop character in this region in all nuclear receptors, with the exception of PPAR provided the foundation of the authors' alternative 'pocket portal' hypothesis (see figures 6 and 7).
Fischer, E. Einfluss der configuration auf die wirkung der enzyme. Ber. Dtsch. Chem. Ges. 27, 2985–2993 (1894).
Koshland, D. E. Jr. Application of a theory of enzyme specificity to protein synthesis. Proc. Natl Acad. Sci. USA 44, 98–104 (1958).
Bursavich, M. G. & Rich, D. H. Designing non-peptide peptidomimetics in the 21st century: inhibitors targeting conformational ensembles. J. Med. Chem. 45, 541–558 (2002). References 59–61 provide an overview of how the theory behind ligand–receptor kinetic models has evolved over time. Of course, many others (such as M. Karplus, J. A. McCammon and H. Gutfreund) have contributed to advancing our understanding of protein dynamics and the physiological and pharmaceutical importance of transitory kinetics.
Lu, G. W. Molecular mechanisms underlying gating activity of voltage dependent ion channels. Sheng Li Ke. Xue. Jin. Zhan. 28, 306–310 (1997).
Catterall, W. A. Molecular mechanisms of gating and drug block of sodium channels. Novartis Found. Symp. 241, 206–218 (2002).
Sadja, R., Smadja, K., Alagem, N. & Reuveny, E. Coupling Gβγ-dependent activation to channel opening via pore elements in inwardly rectifying potassium channels. Neuron 29, 669–680 (2001).
Bond, P. J., Faraldo-Gomez, J. D. & Sansom, M. S. OmpA: a pore or not a pore? Simulation and modeling studies. Biophys. J. 83, 763–775 (2002).
Knowles, J. & Gromo, G. Target selection in drug discovery. Nature Rev. Drug Disov. 2, 63–69 (2003).
Pietras, R. J. & Szego, C. M. Endometrial cell calcium and oestrogen action. Nature 253, 357–359 (1975).
Valverde, M. A. et al. Acute acativation of Maxi-K channels (hSlo) by estradiol binding to the β subunit. Science 285, 1929–1931 (1999).
Simoncini, T. et al. Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature 407, 538–541 (2000).
Razandi, M., Pedram, A. & Levin, E. R. Plasma membrane estrogen receptors signal to antiapoptosis in breast cancer. Mol. Endocrinol. 14, 1434–1447 (2000).
Benten, W. P. et al. Functional testosterone receptors in plasma membranes of T cells. FASEB J. 13, 123–133 (1999).
Benten, W. P. M., Lieberherr, M., Sekeris, C. E. & Wunderlich, F. Testosterone induces Ca2+ influx via non-genomic surface receptors in activated T cells. FEBS Lett. 407, 211–214 (1997).
Lieberherr, M. & Grosse, B. Androgens increase intracellular calcium concentration and inositol 1, 4, 5-trisphosphate and diacylglycerol formation via a pertussis toxin-sensitive G-protein. J. Biol. Chem. 269, 7217–7223 (1994).
Migliaccio, A. et al. Steroid-induced androgen receptor-oestradiol receptor β-Src complex triggers prostate cancer cell proliferation. EMBO J. 19, 5406–5417 (2000).
Estrada, M., Espinosa, A., Muller, M. & Jaimovich, E. Testosterone stimulates intracellular calcium release and mitogen-activated protein kinases via a G protein-coupled receptor in skeletal muscle cells. Endocrinology 144, 3586–3597 (2003).
Bagowski, C. P., Myers, J. W. & Ferrell, J. E. Jr. The classical progesterone receptor associates with p42 MAPK and is involved in phosphatidylinositol 3-kinase signaling in Xenopus oocytes. J. Biol. Chem. 276, 37708–37714 (2001).
Migliaccio, A. et al. Activation of the Src/p21ras/Erk pathway by progesterone receptor via cross-talk with estrogen receptor. EMBO J. 17, 2008–2018 (1998).
Ballare, C. et al. Two domains of the progesterone receptor interact with the estrogen receptor and are required for progesterone activation of the c-Src/Erk pathway in mammalian cells. Mol. Cell Biol. 23, 1994–2008 (2003).
Zanello, L. P. & Norman, A. W. Stimulation by 1α, 25(OH)2-vitamin D3 of whole cell chloride currents in osteoblastic ROS 17/2. 8 cells: a structure-function study. J. Biol. Chem. 272, 22617–22622 (1997). References 21 and 80 are the first reports showing selective activities of 6-s- cis versus 6-s- trans 1α,25(OH) 2 -vitamin D 3 . The cis -locked 1,25(OH) 2 -lumisterol has proven to be instrumental in modelling efforts designed to build a model that provides a plausible explanation for the known activities of this ligand. Many of the non-genomic activities of this ligand have been proposed to be facilitated through the VDR LBD.
Caffrey, J. M. & Farach-Carson, M. C. Vitamin D3 metabolites modulate dihydropyridine-sensitive calcium currents in clonal rat osteosarcoma cells. J. Biol. Chem. 264, 20265–20274 (1989).
Boyan, B. D. et al. Arachidonic acid is an autocoid mediator of the differential action of 1, 25-(OH)2D3 and 24, 25-(OH)2D3 on growth plate chondrocytes. J. Cell. Physiol. 176, 516–524 (1998).
Rebsamen, M. C., Sun, J., Norman, A. W. & Liao, J. K. 1α,25-dihydroxyvitamin D3 induces vascular smooth muscle cell migration via activation of phosphatidylinositol 3-kinase. Circ. Res. 91, 17–24 (2002).
Kajikawa, M. et al. An insulinotropic effect of vitamin D analog with increasing intracellular Ca2+ concentration in pancreatic β-cells through nongenomic signal transduction. Endocrinology 140, 4706–4712 (1999).
Zeitz, U. et al. Impaired insulin secretory capacity in mice lacking a functional vitamin D receptor. FASEB J. 17, 509–511 (2003).
Bhatia, M., Kirkland, J. B. & Meckling-Gill, K. A. Monocytic differentiation of acute promyelocytic leukemia cells in response to 1, 25-dihydroxyvitamin D3 is independent of nuclear receptor binding. J. Biol. Chem. 270, 15962–15965 (1995).
Song, X., Bishop, J. E., Okamura, W. H. & Norman, A. W. Stimulation of phosphorylation of mitogen-activated protein kinase by 1α, 25-dihydroxyvitamin D3 in promyelocytic NB4 leukemia cells: a structure-function study. Endocrinology 139, 457–465 (1998).
Qiu, J. et al. Nongenomic mechanisms of glucocorticoid inhibition of nicotine-induced calcium influx in PC12 cells: involvement of protein kinase C. Endocrinology 139, 5103–5108 (1998).
Orchinik, M., Murray, T. F. & Moore, F. L. A corticosteroid receptor in neuronal membranes. Science 252, 1848–1851 (1991).
Lin, H. Y., Thacorf, H. R., Davis, F. B. & Davis, P. J. Potentiation by thyroxine of interferon-γ-induced antiviral state requires PKA and PKC activities. Am. J. Physiol. Cell Physiol. 271, C1256–C1261 (1996).
Sun, Z. Q. et al. Effects of thyroid hormone on action potential and repolarizing currents in rat ventricular myocytes. Am. J. Physiol. Endocrinol. Metab. 278, E302–E307 (2000).
Davis, P. J. & Davis, F. B. Nongenomic actions of thyroid hormone on the heart. Thyroid 12, 459–466 (2002).
Watson, C. S. & Gametchu, B. Membrane-initiated steroid actions and the proteins that mediate them. Proc. Soc. Exp. Biol. Med. 220, 9–19 (1999).
Falkenstein, E. et al. Multiple actions of steroid hormones a focus on rapid non-genomic effects. Pharmacol. Rev. 52, 513–556 (2000).
Harvey, B. J., Condliffe, S. B. & Doolan, C. M. Sex and salt hormones: rapid effects in epithelia. News Physiol. Sci. 16, 174–177 (2001).
Cato, A. C., Nestl, A. & Mink, S. Rapid actions of steroid receptors in cellular signaling pathways. Science STKE [online], (cited 5 Dec 2003), < http://stke.sciencemag.org/cgi/content/full/sigtrans;2002/138/re9 > (2002).
Losel, R. M. et al. Nongenomic steroid action: controversies, questions, and answers. Physiol. Rev. 83, 965–1016 (2003).
Wong, C. W. et al. Estrogen receptor-interacting protein that modulates its nongenomic activity-crosstalk with Src/Erk phosphorylation cascade. Proc. Natl Acad. Sci. USA 99, 14783–14788 (2002).
Bettoun, D. J. et al. A vitamin D receptor-Ser/Thr phosphatase-p70 S6 kinase complex and modulation of its enzymatic activities by the ligand. J. Biol. Chem. 277, 24847–24850 (2002).
Evans, S. J., Murray, T. F. & Moore, F. L. Partial purification and biochemical characterization of a membrane glucocorticoid receptor from an amphibian brain. J. Steroid. Biochem. Mol. Biol. 72, 209–221 (2000).
Powell, C. E., Watson, C. S. & Gametchu, B. Immunoaffinity isolation of native membrane glucocorticoid receptor from S49++ lymphoma cells: biochemical characterization and interaction with Hsp 70 and Hsp 90. Endocrine 10, 271–280 (1999).
Nemere, I. et al. Identification of a specific binding protein for 1α, 25-dihydroxyvitamin D3 in basal-lateral membranes of chick intestinal epithelium and relationship to transcaltachia. J. Biol. Chem. 269, 23750–23756 (1994).
Nemere, I., Ray, R. & McManus, W. Immunochemical studies on the putative plasmalemmal receptor for 1, 25(OH)(2)D(3). I. Chick intestine. Am. J. Physiol. Endocrinol. Metab. 278, E1104–E1114 (2000).
Boyan, B. D. et al. Evidence for distinct membrane receptors for 1α, 25-(OH)2D3 and 24R, 25-(OH)2D3 in osteoblasts. Steroids 67, 235–246 (2002).
Luconi, M. et al. Characterization of membrane nongenomic receptors for progesterone in human spermatozoa. Steroids 67, 505–509 (2002).
Norfleet, A. M., Thomas, M. L., Gametchu, B. & Watson, C. S. Estrogen receptor-α detected on the plasma membrane of aldehyde-fixed GH3/B6/F10 rat pituitary tumor cells by enzyme-linked immunocytochemistry. Endocrinology 140, 3805–3814 (1999).
Benten, W. P., Stephan, C., Lieberherr, M. & Wunderlich, F. Estradiol signaling via sequestrable surface receptors. Endocrinology 142, 1669–1677 (2001).
Lutz, L. B. et al. Selective modulation of genomic and nongenomic androgen responses by androgen receptor ligands. Mol. Endocrinol. 17, 1106–1116 (2003).
Pietras, R. J. & Szego, C. M. Specific binding site for oestrogen at the outer surfaces of isolated endometrial cells. Nature 265, 69–72 (1977).
Moore, F. L., Orchinik, M. & Lowry, C. Functional studies of corticosterone receptors and neuronal membranes. Receptor 5, 21–28(1995).
Christ, M., Sippel, K., Eisen, C. & Wehling, M. Non-classical receptors for aldosterone in plasma membranes from pig kidneys. Mol. Cell. Endocrinol. 99, R31–R34 (1994).
Kampa, M. et al. The human prostate cancer cell line LNCaP bears functional membrane testosterone receptors that increase PSA secretion and modify actin cytoskeleton. FASEB J. 16, 1429–1431 (2002).
Norfleet, A. M., Clarke, C. H., Gametchu, B. & Watson, C. S. Antibodies to the estrogen receptor-α modulate rapid prolactin release from rat pituitary tumor cells through plasma membrane estrogen receptors. FASEB J. 14, 157–165 (2000).
DiMartino, S. J. & Kew, R. R. Initial characterization of the vitamin D binding protein (Gc-globulin) binding site on the neutrophil plasma membrane: evidence for a chondroitin sulfate proteoglycan. J. Immunol. 163, 2135–2142 (1999).
Rochel, N. et al. The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol. Cell 5, 173–179 (2000). This landmark paper reports the X-ray structure of the VDR LBD complexed to its natural hormone, 1α,25(OH) 2 -vitamin D 3 . The high-resolution X-ray structure provides empirical data that can be used to test structure–function hypotheses relating to the receptor LBD.
Verboven, C. et al. A structural basis for the unique binding features of the human vitamin D-binding protein. Nature Struct. Biol. 9, 131–136 (2002). References 55 and 117 are two break-through papers describing the X-ray structure of two steroid-hormone plasma transport proteins. The structure of the LBDs of these proteins should be contrasted with those of the nuclear receptor LBDs described in references 48, 49 and 116.