NMR assignments and secondary structure of the retinoid X receptor α DNA-binding domain. Evidence for the novel C-terminal helix

M. S. Lee, D. S. Sem, S. A. Kliewer, J. Provencal, R. M. Evans, P. E. Wright

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The retinoid X receptor (RXR) is a member of the nuclear hormone receptor superfamily and has recently been shown to function in a variety of hormonal signaling pathways by virtue of its ability to heterodimerize with other nuclear hormone receptors. Here we describe resonance assignments, the secondary structural elements and the global folding pattern of the DNA-binding domain (residues 130-223) of human RXRα, as determined by multidimensional nuclear magnetic resonance spectroscopy. Its overall structure is similar to those reported for the glucocorticoid, estrogen, and retinoic acid receptors, in that the two zinc fingers of RXR fold to form a single structural domain containing two helices, which are located at the carboxy terminal of the two zinc fingers. There is also a short antiparallel β-sheet formed between two residues in the amino-terminal base of the first finger and two residues in the carboxy terminal of that same finger just before the first helix. However, in contrast to the other nuclear hormone receptor DNA-binding domains, the RXR domain contains a third helix immediately after the conserved Gly-Met sequence that signals the termination of the second helix. The second and third helices lie orthogonal to and wrap around the first helix, generating an extended hydrophobic core. Since helices two and three are separated by only two residues, the backbone flexibility afforded by the presence of the conserved glycine residue between them may be crucial for the proper positioning of the third helix relative to the first helix. A 12-amino-acid region termed the 'T-box', which includes this third helix, was recently shown to be required for homodimeric binding of RXR to its cognate response element [Wilson, T. E., Paulsen, R. E., Padgett, K. A. and Milbrandt, J. (1992) Science 256, 107-110].

Original languageEnglish (US)
Pages (from-to)639-650
Number of pages12
JournalEuropean Journal of Biochemistry
Volume224
Issue number2
StatePublished - 1994

Fingerprint

Retinoid X Receptors
Nuclear magnetic resonance
Cytoplasmic and Nuclear Receptors
DNA
Zinc Fingers
Fingers
Zinc
Retinoic Acid Receptors
Response Elements
Protein Sorting Signals
Glycine
Glucocorticoids
Nuclear magnetic resonance spectroscopy
Estrogens
Magnetic Resonance Spectroscopy
Amino Acids

ASJC Scopus subject areas

  • Biochemistry

Cite this

NMR assignments and secondary structure of the retinoid X receptor α DNA-binding domain. Evidence for the novel C-terminal helix. / Lee, M. S.; Sem, D. S.; Kliewer, S. A.; Provencal, J.; Evans, R. M.; Wright, P. E.

In: European Journal of Biochemistry, Vol. 224, No. 2, 1994, p. 639-650.

Research output: Contribution to journalArticle

@article{d6a660ad3004412b8399702a19979b89,
title = "NMR assignments and secondary structure of the retinoid X receptor α DNA-binding domain. Evidence for the novel C-terminal helix",
abstract = "The retinoid X receptor (RXR) is a member of the nuclear hormone receptor superfamily and has recently been shown to function in a variety of hormonal signaling pathways by virtue of its ability to heterodimerize with other nuclear hormone receptors. Here we describe resonance assignments, the secondary structural elements and the global folding pattern of the DNA-binding domain (residues 130-223) of human RXRα, as determined by multidimensional nuclear magnetic resonance spectroscopy. Its overall structure is similar to those reported for the glucocorticoid, estrogen, and retinoic acid receptors, in that the two zinc fingers of RXR fold to form a single structural domain containing two helices, which are located at the carboxy terminal of the two zinc fingers. There is also a short antiparallel β-sheet formed between two residues in the amino-terminal base of the first finger and two residues in the carboxy terminal of that same finger just before the first helix. However, in contrast to the other nuclear hormone receptor DNA-binding domains, the RXR domain contains a third helix immediately after the conserved Gly-Met sequence that signals the termination of the second helix. The second and third helices lie orthogonal to and wrap around the first helix, generating an extended hydrophobic core. Since helices two and three are separated by only two residues, the backbone flexibility afforded by the presence of the conserved glycine residue between them may be crucial for the proper positioning of the third helix relative to the first helix. A 12-amino-acid region termed the 'T-box', which includes this third helix, was recently shown to be required for homodimeric binding of RXR to its cognate response element [Wilson, T. E., Paulsen, R. E., Padgett, K. A. and Milbrandt, J. (1992) Science 256, 107-110].",
author = "Lee, {M. S.} and Sem, {D. S.} and Kliewer, {S. A.} and J. Provencal and Evans, {R. M.} and Wright, {P. E.}",
year = "1994",
language = "English (US)",
volume = "224",
pages = "639--650",
journal = "FEBS Journal",
issn = "1742-464X",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - NMR assignments and secondary structure of the retinoid X receptor α DNA-binding domain. Evidence for the novel C-terminal helix

AU - Lee, M. S.

AU - Sem, D. S.

AU - Kliewer, S. A.

AU - Provencal, J.

AU - Evans, R. M.

AU - Wright, P. E.

PY - 1994

Y1 - 1994

N2 - The retinoid X receptor (RXR) is a member of the nuclear hormone receptor superfamily and has recently been shown to function in a variety of hormonal signaling pathways by virtue of its ability to heterodimerize with other nuclear hormone receptors. Here we describe resonance assignments, the secondary structural elements and the global folding pattern of the DNA-binding domain (residues 130-223) of human RXRα, as determined by multidimensional nuclear magnetic resonance spectroscopy. Its overall structure is similar to those reported for the glucocorticoid, estrogen, and retinoic acid receptors, in that the two zinc fingers of RXR fold to form a single structural domain containing two helices, which are located at the carboxy terminal of the two zinc fingers. There is also a short antiparallel β-sheet formed between two residues in the amino-terminal base of the first finger and two residues in the carboxy terminal of that same finger just before the first helix. However, in contrast to the other nuclear hormone receptor DNA-binding domains, the RXR domain contains a third helix immediately after the conserved Gly-Met sequence that signals the termination of the second helix. The second and third helices lie orthogonal to and wrap around the first helix, generating an extended hydrophobic core. Since helices two and three are separated by only two residues, the backbone flexibility afforded by the presence of the conserved glycine residue between them may be crucial for the proper positioning of the third helix relative to the first helix. A 12-amino-acid region termed the 'T-box', which includes this third helix, was recently shown to be required for homodimeric binding of RXR to its cognate response element [Wilson, T. E., Paulsen, R. E., Padgett, K. A. and Milbrandt, J. (1992) Science 256, 107-110].

AB - The retinoid X receptor (RXR) is a member of the nuclear hormone receptor superfamily and has recently been shown to function in a variety of hormonal signaling pathways by virtue of its ability to heterodimerize with other nuclear hormone receptors. Here we describe resonance assignments, the secondary structural elements and the global folding pattern of the DNA-binding domain (residues 130-223) of human RXRα, as determined by multidimensional nuclear magnetic resonance spectroscopy. Its overall structure is similar to those reported for the glucocorticoid, estrogen, and retinoic acid receptors, in that the two zinc fingers of RXR fold to form a single structural domain containing two helices, which are located at the carboxy terminal of the two zinc fingers. There is also a short antiparallel β-sheet formed between two residues in the amino-terminal base of the first finger and two residues in the carboxy terminal of that same finger just before the first helix. However, in contrast to the other nuclear hormone receptor DNA-binding domains, the RXR domain contains a third helix immediately after the conserved Gly-Met sequence that signals the termination of the second helix. The second and third helices lie orthogonal to and wrap around the first helix, generating an extended hydrophobic core. Since helices two and three are separated by only two residues, the backbone flexibility afforded by the presence of the conserved glycine residue between them may be crucial for the proper positioning of the third helix relative to the first helix. A 12-amino-acid region termed the 'T-box', which includes this third helix, was recently shown to be required for homodimeric binding of RXR to its cognate response element [Wilson, T. E., Paulsen, R. E., Padgett, K. A. and Milbrandt, J. (1992) Science 256, 107-110].

UR - http://www.scopus.com/inward/record.url?scp=0028141815&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028141815&partnerID=8YFLogxK

M3 - Article

C2 - 7925381

AN - SCOPUS:0028141815

VL - 224

SP - 639

EP - 650

JO - FEBS Journal

JF - FEBS Journal

SN - 1742-464X

IS - 2

ER -