Retinoid X Receptor Alpha Forms Tetramers in Solution

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1995 Sep 12

PMID 7567990

Citations 25

Authors

S Kersten

D Kelleher

P Chambon

H Gronemeyer

N Noy

Affiliations

Soon will be listed here.

Abstract

Protein-protein interactions allow the retinoid X receptor (RXR) to bind to cognate DNA as a homo- or a heterodimer and to participate in mediating the effects of a variety of hormones on gene transcription. Here we report a systematic study of the oligomeric state of RXR in the absence of a DNA template. We have used electrophoresis under nondenaturing conditions and chemical crosslinking to show that in solution, RXR alpha forms homodimers as well as homotetramers. The dissociation constants governing dimer and tetramer formation were estimated by fluorescence anisotropy studies. The results indicate that RXR tetramers are formed with a high affinity and that at protein concentrations higher than about 70 nM, tetramers will constitute the predominant species. Tetramer formation may provide an additional level of the regulation of gene transcription mediated by RXRs.

Citing Articles

Molecular basis of ligand-dependent Nurr1-RXRα activation.

Yu X, Shang J, Kojetin D Elife. 2023; 12.

PMID: 37102494 PMC: 10259986. DOI: 10.7554/eLife.85039.

A structural signature motif enlightens the origin and diversification of nuclear receptors.

Beinsteiner B, Markov G, Erb S, Chebaro Y, McEwen A, Cianferani S PLoS Genet. 2021; 17(4):e1009492.

PMID: 33882063 PMC: 8092661. DOI: 10.1371/journal.pgen.1009492.

Glucocorticoid receptor quaternary structure drives chromatin occupancy and transcriptional outcome.

Paakinaho V, Johnson T, Presman D, Hager G Genome Res. 2019; 29(8):1223-1234.

PMID: 31337711 PMC: 6673716. DOI: 10.1101/gr.244814.118.

Retinoid X Receptor Antagonists.

Watanabe M, Kakuta H Int J Mol Sci. 2018; 19(8).

PMID: 30103423 PMC: 6121510. DOI: 10.3390/ijms19082354.

Translation of a Tissue-Selective Rexinoid, UAB30, to the Clinic for Breast Cancer Prevention.

Muccio D, Atigadda V, Brouillette W, Bland K, Krontiras H, Grubbs C Curr Top Med Chem. 2016; 17(6):676-695.

PMID: 27320329 PMC: 9904082. DOI: 10.2174/1568026616666160617093604.

References

Zechel C, Shen X, Chambon P, Gronemeyer H . Dimerization interfaces formed between the DNA binding domains determine the cooperative binding of RXR/RAR and RXR/TR heterodimers to DR5 and DR4 elements. EMBO J. 1994; 13(6):1414-24. PMC: 394959. DOI: 10.1002/j.1460-2075.1994.tb06395.x. View

Chen H, Privalsky M . Cooperative formation of high-order oligomers by retinoid X receptors: an unexpected mode of DNA recognition. Proc Natl Acad Sci U S A. 1995; 92(2):422-6. PMC: 42752. DOI: 10.1073/pnas.92.2.422. View

Chen Z, Shemshedini L, Durand B, Noy N, Chambon P, Gronemeyer H . Pure and functionally homogeneous recombinant retinoid X receptor. J Biol Chem. 1994; 269(41):25770-6. View

Nervi C, Grippo J, Sherman M, George M, Jetten A . Identification and characterization of nuclear retinoic acid-binding activity in human myeloblastic leukemia HL-60 cells. Proc Natl Acad Sci U S A. 1989; 86(15):5854-8. PMC: 297729. DOI: 10.1073/pnas.86.15.5854. View

Sorger P, NELSON H . Trimerization of a yeast transcriptional activator via a coiled-coil motif. Cell. 1989; 59(5):807-13. DOI: 10.1016/0092-8674(89)90604-1. View

Mangelsdorf D, Ong E, Dyck J, Evans R . Nuclear receptor that identifies a novel retinoic acid response pathway. Nature. 1990; 345(6272):224-9. DOI: 10.1038/345224a0. View

Forman B, Samuels H . Interactions among a subfamily of nuclear hormone receptors: the regulatory zipper model. Mol Endocrinol. 1990; 4(9):1293-301. DOI: 10.1210/mend-4-9-1293. View

ROYER C, Smith W, Beechem J . Analysis of binding in macromolecular complexes: a generalized numerical approach. Anal Biochem. 1990; 191(2):287-94. DOI: 10.1016/0003-2697(90)90221-t. View

Levin A, Sturzenbecker L, Kazmer S, Bosakowski T, Huselton C, Allenby G . 9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR alpha. Nature. 1992; 355(6358):359-61. DOI: 10.1038/355359a0. View

10.

Leid M, Kastner P, Lyons R, Nakshatri H, Saunders M, Zacharewski T . Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell. 1992; 68(2):377-95. DOI: 10.1016/0092-8674(92)90478-u. View

11.

HEYMAN R, Mangelsdorf D, Dyck J, Stein R, Eichele G, Evans R . 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell. 1992; 68(2):397-406. DOI: 10.1016/0092-8674(92)90479-v. View

12.

Fernando T, Royer C . Role of protein--protein interactions in the regulation of transcription by trp repressor investigated by fluorescence spectroscopy. Biochemistry. 1992; 31(13):3429-41. DOI: 10.1021/bi00128a018. View

13.

Zhang X, Lehmann J, Hoffmann B, Dawson M, Cameron J, Graupner G . Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid. Nature. 1992; 358(6387):587-91. DOI: 10.1038/358587a0. View

14.

Hurlburt B, Yanofsky C . trp repressor/trp operator interaction. Equilibrium and kinetic analysis of complex formation and stability. J Biol Chem. 1992; 267(24):16783-9. View

15.

Noy N, Slosberg E, Scarlata S . Interactions of retinol with binding proteins: studies with retinol-binding protein and with transthyretin. Biochemistry. 1992; 31(45):11118-24. DOI: 10.1021/bi00160a023. View

16.

Mader S, Leroy P, Chen J, Chambon P . Multiple parameters control the selectivity of nuclear receptors for their response elements. Selectivity and promiscuity in response element recognition by retinoic acid receptors and retinoid X receptors. J Biol Chem. 1993; 268(1):591-600. View

17.

Ayer D, Kretzner L, Eisenman R . Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity. Cell. 1993; 72(2):211-22. DOI: 10.1016/0092-8674(93)90661-9. View

18.

Perlmann T, Rangarajan P, Umesono K, Evans R . Determinants for selective RAR and TR recognition of direct repeat HREs. Genes Dev. 1993; 7(7B):1411-22. DOI: 10.1101/gad.7.7b.1411. View

19.

Kurokawa R, Yu V, NAAR A, Kyakumoto S, Han Z, Silverman S . Differential orientations of the DNA-binding domain and carboxy-terminal dimerization interface regulate binding site selection by nuclear receptor heterodimers. Genes Dev. 1993; 7(7B):1423-35. DOI: 10.1101/gad.7.7b.1423. View

20.

LeTilly V, ROYER C . Fluorescence anisotropy assays implicate protein-protein interactions in regulating trp repressor DNA binding. Biochemistry. 1993; 32(30):7753-8. DOI: 10.1021/bi00081a021. View