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* Residue conservation analysis
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Enzyme class:
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Chains A, B:
E.C.?
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DOI no:
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Mol Cell
5:289-298
(2000)
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PubMed id:
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Crystal structure of a heterodimeric complex of RAR and RXR ligand-binding domains.
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W.Bourguet,
V.Vivat,
J.M.Wurtz,
P.Chambon,
H.Gronemeyer,
D.Moras.
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ABSTRACT
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The crystal structure of a heterodimer between the ligand-binding domains (LBDs)
of the human RARalpha bound to a selective antagonist and the constitutively
active mouse RXRalphaF318A mutant shows that, pushed by a bulky extension of the
ligand, RARalpha helix H12 adopts an antagonist position. The unexpected
presence of a fatty acid in the ligand-binding pocket of RXRalpha(F318A is
likely to account for its apparent "constitutivity." Specific
conformational changes suggest the structural basis of pure and partial
antagonism. The RAR-RXR heterodimer interface is similar to that observed in
most nuclear receptor (NR) homodimers. A correlative analysis of 3D structures
and sequences provides a novel view on dimerization among members of the nuclear
receptor superfamily.
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Selected figure(s)
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Figure 1.
Figure 1. The RARα–RXRαF318A LBD Heterodimer and Its
Component Monomers(A) The dimeric arrangement of hRARα and
mRXRαF318A LBDs is viewed perpendicular to the dimer axis. The
secondary structural elements are labeled according to the
nomenclature of other nuclear receptors ([38]). Helices (H) are
represented as tubes; coil regions are colored in orange; β
strands (s) in red. The dotted line in mRXRαF318A indicates the
unmodeled region between H1 and H3. The ligands in hRARα
(BMS614) and mRXRαF318A (oleic acid, OA) are represented in
yellow.(B) Superposition of the hRARα/BMS614 complex from the
heterodimer crystal structure and the hRARγ/T-RA monomer
complex ([26]).(C) Superposition of the mRXRαF318A/OA LBD from
the heterodimer crystal structure and the hRXRα/9C-RA LBD
monomer crystal structure (P. Egea et al., submitted).(D)
Superposition of the hRARα/BMS614 and the mRXRαF318A/OA LBD
complexes, both from the heterodimer crystal structure.
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Figure 4.
Figure 4. The mRXRαF318A Ligand-Binding Pocket(A) Oleic
acid (OA) interactions with the mRXRαF318A LBD. Interactions
between the protein and the ligand (4.2 Å cutoff) are
depicted as broken lines. Residue names are colored as a
function of the mRXRαF318A structural element from which they
originate. W indicates a water molecule.(B) Stereo view of the
2.5 Å resolution (2F[o]-F[c]) map contoured at 1.0
standard deviation, with OA docked into its binding site. The
protein Cα trace is represented in gray, the contacting side
chains (carbons, yellow; oxygen, red; nitrogen, blue; sulphur,
green) and the ligand (blue) by thick lines.(C) Superposition of
the ligand-binding sites of the mRXRαF318A/OA (blue) and the
hRXRα/9C-RA (pink) LBDs. The gray arrows highlight the
different ligand-specific induced conformations in both
complexes. Helices (ribbons) and loops (rods) are indicated, as
well as some residues (mouse RXRα numbering) discussed in the
text.
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2000,
5,
289-298)
copyright 2000.
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Figures were
selected
by the author.
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Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
J.Zhang,
M.J.Chalmers,
K.R.Stayrook,
L.L.Burris,
Y.Wang,
S.A.Busby,
B.D.Pascal,
R.D.Garcia-Ordonez,
J.B.Bruning,
M.A.Istrate,
D.J.Kojetin,
J.A.Dodge,
T.P.Burris,
and
P.R.Griffin
(2011).
DNA binding alters coactivator interaction surfaces of the intact VDR-RXR complex.
|
| |
Nat Struct Mol Biol,
18,
556-563.
|
|
|
|
|
|
|
L.P.Albou,
O.Poch,
and
D.Moras
(2011).
M-ORBIS: mapping of molecular binding sites and surfaces.
|
| |
Nucleic Acids Res,
39,
30-43.
|
|
|
|
|
|
|
N.Rochel,
F.Ciesielski,
J.Godet,
E.Moman,
M.Roessle,
C.Peluso-Iltis,
M.Moulin,
M.Haertlein,
P.Callow,
Y.Mély,
D.I.Svergun,
and
D.Moras
(2011).
Common architecture of nuclear receptor heterodimers on DNA direct repeat elements with different spacings.
|
| |
Nat Struct Mol Biol,
18,
564-570.
|
|
|
|
|
|
|
A.le Maire,
C.Teyssier,
C.Erb,
M.Grimaldi,
S.Alvarez,
A.R.de Lera,
P.Balaguer,
H.Gronemeyer,
C.A.Royer,
P.Germain,
and
W.Bourguet
(2010).
A unique secondary-structure switch controls constitutive gene repression by retinoic acid receptor.
|
| |
Nat Struct Mol Biol,
17,
801-807.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
C.Schinke,
S.Goel,
T.D.Bhagat,
L.Zhou,
Y.Mo,
R.Gallagher,
G.W.Kabalka,
L.C.Platanias,
A.Verma,
and
B.Das
(2010).
Design and synthesis of novel derivatives of all-trans retinoic acid demonstrate the combined importance of acid moiety and conjugated double bonds in its binding to PML-RAR-alpha oncogene in acute promyelocytic leukemia.
|
| |
Leuk Lymphoma,
51,
1108-1114.
|
|
|
|
|
|
|
H.Zhou,
W.Liu,
Y.Su,
Z.Wei,
J.Liu,
S.K.Kolluri,
H.Wu,
Y.Cao,
J.Chen,
Y.Wu,
T.Yan,
X.Cao,
W.Gao,
A.Molotkov,
F.Jiang,
W.G.Li,
B.Lin,
H.P.Zhang,
J.Yu,
S.P.Luo,
J.Z.Zeng,
G.Duester,
P.Q.Huang,
and
X.K.Zhang
(2010).
NSAID sulindac and its analog bind RXRalpha and inhibit RXRalpha-dependent AKT signaling.
|
| |
Cancer Cell,
17,
560-573.
|
|
|
|
|
|
|
L.Jin,
and
Y.Li
(2010).
Structural and functional insights into nuclear receptor signaling.
|
| |
Adv Drug Deliv Rev,
62,
1218-1226.
|
|
|
|
|
|
|
M.Theodosiou,
V.Laudet,
and
M.Schubert
(2010).
From carrot to clinic: an overview of the retinoic acid signaling pathway.
|
| |
Cell Mol Life Sci,
67,
1423-1445.
|
|
|
|
|
|
|
N.Noy
(2010).
Between death and survival: retinoic acid in regulation of apoptosis.
|
| |
Annu Rev Nutr,
30,
201-217.
|
|
|
|
|
|
|
N.Shibata,
and
C.K.Glass
(2010).
Macrophages, oxysterols and atherosclerosis.
|
| |
Circ J,
74,
2045-2051.
|
|
|
|
|
|
|
P.Huang,
V.Chandra,
and
F.Rastinejad
(2010).
Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics.
|
| |
Annu Rev Physiol,
72,
247-272.
|
|
|
|
|
|
|
Y.Sato,
N.Ramalanjaona,
T.Huet,
N.Potier,
J.Osz,
P.Antony,
C.Peluso-Iltis,
P.Poussin-Courmontagne,
E.Ennifar,
Y.Mély,
A.Dejaegere,
D.Moras,
and
N.Rochel
(2010).
The "Phantom Effect" of the Rexinoid LG100754: structural and functional insights.
|
| |
PLoS One,
5,
e15119.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
C.Rochette-Egly,
and
P.Germain
(2009).
Dynamic and combinatorial control of gene expression by nuclear retinoic acid receptors (RARs).
|
| |
Nucl Recept Signal,
7,
e005.
|
|
|
|
|
|
|
G.D.Tocchini-Valentini,
N.Rochel,
H.Escriva,
P.Germain,
C.Peluso-Iltis,
M.Paris,
S.Sanglier-Cianferani,
A.Van Dorsselaer,
D.Moras,
and
V.Laudet
(2009).
Structural and functional insights into the ligand-binding domain of a nonduplicated retinoid X nuclear receptor from the invertebrate chordate amphioxus.
|
| |
J Biol Chem,
284,
1938-1948.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
J.Lu,
M.I.Dawson,
Q.Y.Hu,
Z.Xia,
J.D.Dambacher,
M.Ye,
X.K.Zhang,
and
E.Li
(2009).
The effect of antagonists on the conformational exchange of the retinoid X receptor alpha ligand-binding domain.
|
| |
Magn Reson Chem,
47,
1071-1080.
|
|
|
|
|
|
|
L.S.Chan,
and
R.A.Wells
(2009).
Cross-Talk between PPARs and the Partners of RXR: A Molecular Perspective.
|
| |
PPAR Res,
2009,
925309.
|
|
|
|
|
|
|
M.E.Harder,
D.A.Malencik,
X.Yan,
D.Broderick,
M.Leid,
S.R.Anderson,
M.L.Deinzer,
and
M.I.Schimerlik
(2009).
Equilibrium unfolding of the retinoid X receptor ligand binding domain and characterization of an unfolding intermediate.
|
| |
Biophys Chem,
141,
1.
|
|
|
|
|
|
|
S.Pérez-Rodríguez,
M.A.Ortiz,
R.Pereira,
F.Rodríguez-Barrios,
A.R.de Lera,
and
F.J.Piedrafita
(2009).
Highly twisted adamantyl arotinoids: synthesis, antiproliferative effects and RXR transactivation profiles.
|
| |
Eur J Med Chem,
44,
2434-2446.
|
|
|
|
|
|
|
T.Iwema,
A.Chaumot,
R.A.Studer,
M.Robinson-Rechavi,
I.M.Billas,
D.Moras,
V.Laudet,
and
F.Bonneton
(2009).
Structural and evolutionary innovation of the heterodimerization interface between USP and the ecdysone receptor ECR in insects.
|
| |
Mol Biol Evol,
26,
753-768.
|
|
|
|
|
|
|
X.Yuan,
T.C.Ta,
M.Lin,
J.R.Evans,
Y.Dong,
E.Bolotin,
M.A.Sherman,
B.M.Forman,
and
F.M.Sladek
(2009).
Identification of an endogenous ligand bound to a native orphan nuclear receptor.
|
| |
PLoS ONE,
4,
e5609.
|
|
|
|
|
|
|
Y.H.Han,
H.Zhou,
J.H.Kim,
T.D.Yan,
K.H.Lee,
H.Wu,
F.Lin,
N.Lu,
J.Liu,
J.Z.Zeng,
and
X.K.Zhang
(2009).
A Unique Cytoplasmic Localization of Retinoic Acid Receptor-{gamma} and Its Regulations.
|
| |
J Biol Chem,
284,
18503-18514.
|
|
|
|
|
|
|
J.Zhang,
and
D.S.Geller
(2008).
Helix 3-helix 5 interactions in steroid hormone receptor function.
|
| |
J Steroid Biochem Mol Biol,
109,
279-285.
|
|
|
|
|
|
|
L.M.Sanderson,
P.J.de Groot,
G.J.Hooiveld,
A.Koppen,
E.Kalkhoven,
M.Müller,
and
S.Kersten
(2008).
Effect of synthetic dietary triglycerides: a novel research paradigm for nutrigenomics.
|
| |
PLoS ONE,
3,
e1681.
|
|
|
|
|
|
|
M.D.Krasowski,
E.J.Reschly,
and
S.Ekins
(2008).
Intrinsic disorder in nuclear hormone receptors.
|
| |
J Proteome Res,
7,
4359-4372.
|
|
|
|
|
|
|
R.Minai,
Y.Matsuo,
H.Onuki,
and
H.Hirota
(2008).
Method for comparing the structures of protein ligand-binding sites and application for predicting protein-drug interactions.
|
| |
Proteins,
72,
367-381.
|
|
|
|
|
|
|
S.W.Kruse,
K.Suino-Powell,
X.E.Zhou,
J.E.Kretschman,
R.Reynolds,
C.Vonrhein,
Y.Xu,
L.Wang,
S.Y.Tsai,
M.J.Tsai,
and
H.E.Xu
(2008).
Identification of COUP-TFII orphan nuclear receptor as a retinoic acid-activated receptor.
|
| |
PLoS Biol,
6,
e227.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
V.Nahoum,
A.Lipski,
F.Quillard,
J.F.Guichou,
Y.Boublik,
E.Pérez,
P.Germain,
A.R.de Lera,
and
W.Bourguet
(2008).
Nuclear receptor ligand-binding domains: reduction of helix H12 dynamics to favour crystallization.
|
| |
Acta Crystallogr Sect F Struct Biol Cryst Commun,
64,
614-616.
|
|
|
|
|
|
|
Y.Umezawa
(2008).
Detecting mitochondrial RNA and other cellular events in living cells.
|
| |
Anal Bioanal Chem,
391,
1591-1598.
|
|
|
|
|
|
|
A.R.de Lera,
W.Bourguet,
L.Altucci,
and
H.Gronemeyer
(2007).
Design of selective nuclear receptor modulators: RAR and RXR as a case study.
|
| |
Nat Rev Drug Discov,
6,
811-820.
|
|
|
|
|
|
|
C.Browning,
E.Martin,
C.Loch,
J.M.Wurtz,
D.Moras,
R.H.Stote,
A.P.Dejaegere,
and
I.M.Billas
(2007).
Critical role of desolvation in the binding of 20-hydroxyecdysone to the ecdysone receptor.
|
| |
J Biol Chem,
282,
32924-32934.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
M.Awais,
M.Sato,
and
Y.Umezawa
(2007).
Imaging of selective nuclear receptor modulator-induced conformational changes in the nuclear receptor to allow interaction with coactivator and corepressor proteins in living cells.
|
| |
Chembiochem,
8,
737-743.
|
|
|
|
|
|
|
M.Fradot,
O.Lorentz,
J.M.Wurtz,
J.A.Sahel,
and
T.Léveillard
(2007).
The loss of transcriptional inhibition by the photoreceptor-cell specific nuclear receptor (NR2E3) is not a necessary cause of enhanced S-cone syndrome.
|
| |
Mol Vis,
13,
594-601.
|
|
|
|
|
|
|
N.Heldring,
T.Pawson,
D.McDonnell,
E.Treuter,
J.A.Gustafsson,
and
A.C.Pike
(2007).
Structural insights into corepressor recognition by antagonist-bound estrogen receptors.
|
| |
J Biol Chem,
282,
10449-10455.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
P.Hu,
M.Zhang,
and
J.L.Napoli
(2007).
Ontogeny of rdh9 (Crad3) expression: ablation causes changes in retinoid and steroid metabolizing enzymes, but RXR and androgen signaling seem normal.
|
| |
Biochim Biophys Acta,
1770,
694-705.
|
|
|
|
|
|
|
S.Alvarez,
P.Germain,
R.Alvarez,
F.Rodríguez-Barrios,
H.Gronemeyer,
and
A.R.de Lera
(2007).
Structure, function and modulation of retinoic acid receptor beta, a tumor suppressor.
|
| |
Int J Biochem Cell Biol,
39,
1406-1415.
|
|
|
|
|
|
|
W.Wu,
E.G.Niles,
H.Hirai,
and
P.T.LoVerde
(2007).
Evolution of a novel subfamily of nuclear receptors with members that each contain two DNA binding domains.
|
| |
BMC Evol Biol,
7,
27.
|
|
|
|
|
|
|
X.K.Zhang
(2007).
Targeting Nur77 translocation.
|
| |
Expert Opin Ther Targets,
11,
69-79.
|
|
|
|
|
|
|
E.Gaillard,
N.Bruck,
Y.Brelivet,
G.Bour,
S.Lalevée,
A.Bauer,
O.Poch,
D.Moras,
and
C.Rochette-Egly
(2006).
Phosphorylation by PKA potentiates retinoic acid receptor alpha activity by means of increasing interaction with and phosphorylation by cyclin H/cdk7.
|
| |
Proc Natl Acad Sci U S A,
103,
9548-9553.
|
|
|
|
|
|
|
F.Piu,
N.K.Gauthier,
and
F.Wang
(2006).
Beta-arrestin 2 modulates the activity of nuclear receptor RAR beta2 through activation of ERK2 kinase.
|
| |
Oncogene,
25,
218-229.
|
|
|
|
|
|
|
G.Jones,
D.Jones,
P.Teal,
A.Sapa,
and
M.Wozniak
(2006).
The retinoid-X receptor ortholog, ultraspiracle, binds with nanomolar affinity to an endogenous morphogenetic ligand.
|
| |
FEBS J,
273,
4983-4996.
|
|
|
|
|
|
|
G.Wolf
(2006).
Is 9-cis-retinoic acid the endogenous ligand for the retinoic acid-X receptor?
|
| |
Nutr Rev,
64,
532-538.
|
|
|
|
|
|
|
J.Beatty,
T.Fauth,
J.L.Callender,
M.Spindler-Barth,
and
V.C.Henrich
(2006).
Analysis of transcriptional activity mediated by Drosophila melanogaster ecdysone receptor isoforms in a heterologous cell culture system.
|
| |
Insect Mol Biol,
15,
785-795.
|
|
|
|
|
|
|
M.Awais,
M.Sato,
X.Lee,
and
Y.Umezawa
(2006).
A fluorescent indicator to visualize activities of the androgen receptor ligands in single living cells.
|
| |
Angew Chem Int Ed Engl,
45,
2707-2712.
|
|
|
|
|
|
|
F.Fang,
Y.Xu,
D.Jones,
and
G.Jones
(2005).
Interactions of ultraspiracle with ecdysone receptor in the transduction of ecdysone- and juvenile hormone-signaling.
|
| |
FEBS J,
272,
1577-1589.
|
|
|
|
|
|
|
G.Bour,
E.Gaillard,
N.Bruck,
S.Lalevée,
J.L.Plassat,
D.Busso,
J.P.Samama,
and
C.Rochette-Egly
(2005).
Cyclin H binding to the RARalpha activation function (AF)-2 domain directs phosphorylation of the AF-1 domain by cyclin-dependent kinase 7.
|
| |
Proc Natl Acad Sci U S A,
102,
16608-16613.
|
|
|
|
|
|
|
J.A.Carmichael,
M.C.Lawrence,
L.D.Graham,
P.A.Pilling,
V.C.Epa,
L.Noyce,
G.Lovrecz,
D.A.Winkler,
A.Pawlak-Skrzecz,
R.E.Eaton,
G.N.Hannan,
and
R.J.Hill
(2005).
The X-ray structure of a hemipteran ecdysone receptor ligand-binding domain: comparison with a lepidopteran ecdysone receptor ligand-binding domain and implications for insecticide design.
|
| |
J Biol Chem,
280,
22258-22269.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
J.Zhang,
J.Simisky,
F.T.Tsai,
and
D.S.Geller
(2005).
A critical role of helix 3-helix 5 interaction in steroid hormone receptor function.
|
| |
Proc Natl Acad Sci U S A,
102,
2707-2712.
|
|
|
|
|
|
|
K.W.Nettles,
and
G.L.Greene
(2005).
Ligand control of coregulator recruitment to nuclear receptors.
|
| |
Annu Rev Physiol,
67,
309-333.
|
|
|
|
|
|
|
M.Togashi,
P.Nguyen,
R.Fletterick,
J.D.Baxter,
and
P.Webb
(2005).
Rearrangements in thyroid hormone receptor charge clusters that stabilize bound 3,5',5-triiodo-L-thyronine and inhibit homodimer formation.
|
| |
J Biol Chem,
280,
25665-25673.
|
|
|
|
|
|
|
P.Gu,
D.H.Morgan,
M.Sattar,
X.Xu,
R.Wagner,
M.Raviscioni,
O.Lichtarge,
and
A.J.Cooney
(2005).
Evolutionary trace-based peptides identify a novel asymmetric interaction that mediates oligomerization in nuclear receptors.
|
| |
J Biol Chem,
280,
31818-31829.
|
|
|
|
|
|
|
R.Flaig,
H.Greschik,
C.Peluso-Iltis,
and
D.Moras
(2005).
Structural basis for the cell-specific activities of the NGFI-B and the Nurr1 ligand-binding domain.
|
| |
J Biol Chem,
280,
19250-19258.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
R.Yasmin,
R.M.Williams,
M.Xu,
and
N.Noy
(2005).
Nuclear import of the retinoid X receptor, the vitamin D receptor, and their mutual heterodimer.
|
| |
J Biol Chem,
280,
40152-40160.
|
|
|
|
|
|
|
S.C.Perera,
S.Zheng,
Q.L.Feng,
P.J.Krell,
A.Retnakaran,
and
S.R.Palli
(2005).
Heterodimerization of ecdysone receptor and ultraspiracle on symmetric and asymmetric response elements.
|
| |
Arch Insect Biochem Physiol,
60,
55-70.
|
|
|
|
|
|
|
S.Lee,
and
M.L.Privalsky
(2005).
Heterodimers of retinoic acid receptors and thyroid hormone receptors display unique combinatorial regulatory properties.
|
| |
Mol Endocrinol,
19,
863-878.
|
|
|
|
|
|
|
V.Pogenberg,
J.F.Guichou,
V.Vivat-Hannah,
S.Kammerer,
E.Pérez,
P.Germain,
A.R.de Lera,
H.Gronemeyer,
C.A.Royer,
and
W.Bourguet
(2005).
Characterization of the interaction between retinoic acid receptor/retinoid X receptor (RAR/RXR) heterodimers and transcriptional coactivators through structural and fluorescence anisotropy studies.
|
| |
J Biol Chem,
280,
1625-1633.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
W.Wang,
C.Zhang,
A.Marimuthu,
H.I.Krupka,
M.Tabrizizad,
R.Shelloe,
U.Mehra,
K.Eng,
H.Nguyen,
C.Settachatgul,
B.Powell,
M.V.Milburn,
and
B.L.West
(2005).
The crystal structures of human steroidogenic factor-1 and liver receptor homologue-1.
|
| |
Proc Natl Acad Sci U S A,
102,
7505-7510.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
A.F.Valledor,
L.C.Hsu,
S.Ogawa,
D.Sawka-Verhelle,
M.Karin,
and
C.K.Glass
(2004).
Activation of liver X receptors and retinoid X receptors prevents bacterial-induced macrophage apoptosis.
|
| |
Proc Natl Acad Sci U S A,
101,
17813-17818.
|
|
|
|
|
|
|
H.Liu,
C.K.Shaw,
E.L.Reineke,
Y.Liu,
and
H.Y.Kao
(2004).
Retinoid X receptor alpha (RXRalpha) helix 12 plays an inhibitory role in the recruitment of the p160 co-activators by unliganded RXRalpha/retinoic acid receptor alpha heterodimers.
|
| |
J Biol Chem,
279,
45208-45218.
|
|
|
|
|
|
|
K.Suino,
L.Peng,
R.Reynolds,
Y.Li,
J.Y.Cha,
J.J.Repa,
S.A.Kliewer,
and
H.E.Xu
(2004).
The nuclear xenobiotic receptor CAR: structural determinants of constitutive activation and heterodimerization.
|
| |
Mol Cell,
16,
893-905.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
K.W.Nettles,
J.Sun,
J.T.Radek,
S.Sheng,
A.L.Rodriguez,
J.A.Katzenellenbogen,
B.S.Katzenellenbogen,
and
G.L.Greene
(2004).
Allosteric control of ligand selectivity between estrogen receptors alpha and beta: implications for other nuclear receptors.
|
| |
Mol Cell,
13,
317-327.
|
|
|
|
|
|
|
M.L.Privalsky
(2004).
The role of corepressors in transcriptional regulation by nuclear hormone receptors.
|
| |
Annu Rev Physiol,
66,
315-360.
|
|
|
|
|
|
|
P.Germain,
S.Kammerer,
E.Pérez,
C.Peluso-Iltis,
D.Tortolani,
F.C.Zusi,
J.Starrett,
P.Lapointe,
J.P.Daris,
A.Marinier,
A.R.de Lera,
N.Rochel,
and
H.Gronemeyer
(2004).
Rational design of RAR-selective ligands revealed by RARbeta crystal stucture.
|
| |
EMBO Rep,
5,
877-882.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
R.X.Xu,
M.H.Lambert,
B.B.Wisely,
E.N.Warren,
E.E.Weinert,
G.M.Waitt,
J.D.Williams,
J.L.Collins,
L.B.Moore,
T.M.Willson,
and
J.T.Moore
(2004).
A structural basis for constitutive activity in the human CAR/RXRalpha heterodimer.
|
| |
Mol Cell,
16,
919-928.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
S.Kammerer,
P.Germain,
R.Flaig,
C.Peluso-Iltis,
A.Mitschler,
N.Rochel,
H.Gronemeyer,
and
D.Moras
(2004).
RARbeta ligand-binding domain bound to an SRC-1 co-activator peptide: purification, crystallization and preliminary X-ray diffraction analysis.
|
| |
Acta Crystallogr D Biol Crystallogr,
60,
2048-2050.
|
|
|
|
|
|
|
S.Sanglier,
W.Bourguet,
P.Germain,
V.Chavant,
D.Moras,
H.Gronemeyer,
N.Potier,
and
A.Van Dorsselaer
(2004).
Monitoring ligand-mediated nuclear receptor-coregulator interactions by noncovalent mass spectrometry.
|
| |
Eur J Biochem,
271,
4958-4967.
|
|
|
|
|
|
|
V.Pogenberg,
J.F.Guichou,
and
W.Bourguet
(2004).
Purification and crystallization of the heterodimeric complex of RARbeta and RXRalpha ligand-binding domains in the active conformation.
|
| |
Acta Crystallogr D Biol Crystallogr,
60,
1170-1172.
|
|
|
|
|
|
|
X.Cao,
W.Liu,
F.Lin,
H.Li,
S.K.Kolluri,
B.Lin,
Y.H.Han,
M.I.Dawson,
and
X.K.Zhang
(2004).
Retinoid X receptor regulates Nur77/TR3-dependent apoptosis [corrected] by modulating its nuclear export and mitochondrial targeting.
|
| |
Mol Cell Biol,
24,
9705-9725.
|
|
|
|
|
|
|
Y.Brelivet,
S.Kammerer,
N.Rochel,
O.Poch,
and
D.Moras
(2004).
Signature of the oligomeric behaviour of nuclear receptors at the sequence and structural level.
|
| |
EMBO Rep,
5,
423-429.
|
|
|
|
|
|
|
B.C.Kallenberger,
J.D.Love,
V.K.Chatterjee,
and
J.W.Schwabe
(2003).
A dynamic mechanism of nuclear receptor activation and its perturbation in a human disease.
|
| |
Nat Struct Biol,
10,
136-140.
|
|
|
|
|
|
|
B.Farboud,
H.Hauksdottir,
Y.Wu,
and
M.L.Privalsky
(2003).
Isotype-restricted corepressor recruitment: a constitutively closed helix 12 conformation in retinoic acid receptors beta and gamma interferes with corepressor recruitment and prevents transcriptional repression.
|
| |
Mol Cell Biol,
23,
2844-2858.
|
|
|
|
|
|
|
C.Stehlin-Gaon,
D.Willmann,
D.Zeyer,
S.Sanglier,
A.Van Dorsselaer,
J.P.Renaud,
D.Moras,
and
R.Schüle
(2003).
All-trans retinoic acid is a ligand for the orphan nuclear receptor ROR beta.
|
| |
Nat Struct Biol,
10,
820-825.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
H.Y.Kao,
C.C.Han,
A.A.Komar,
and
R.M.Evans
(2003).
Co-repressor release but not ligand binding is a prerequisite for transcription activation by human retinoid acid receptor alpha ligand-binding domain.
|
| |
J Biol Chem,
278,
7366-7373.
|
|
|
|
|
|
|
I.M.Billas,
T.Iwema,
J.M.Garnier,
A.Mitschler,
N.Rochel,
and
D.Moras
(2003).
Structural adaptability in the ligand-binding pocket of the ecdysone hormone receptor.
|
| |
Nature,
426,
91-96.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
J.B.Barry,
G.M.Leong,
W.B.Church,
L.L.Issa,
J.A.Eisman,
and
E.M.Gardiner
(2003).
Interactions of SKIP/NCoA-62, TFIIB, and retinoid X receptor with vitamin D receptor helix H10 residues.
|
| |
J Biol Chem,
278,
8224-8228.
|
|
|
|
|
|
|
J.Eeckhoute,
B.Oxombre,
P.Formstecher,
P.Lefebvre,
and
B.Laine
(2003).
Critical role of charged residues in helix 7 of the ligand binding domain in Hepatocyte Nuclear Factor 4alpha dimerisation and transcriptional activity.
|
| |
Nucleic Acids Res,
31,
6640-6650.
|
|
|
|
|
|
|
K.D.Baker,
L.M.Shewchuk,
T.Kozlova,
M.Makishima,
A.Hassell,
B.Wisely,
J.A.Caravella,
M.H.Lambert,
J.L.Reinking,
H.Krause,
C.S.Thummel,
T.M.Willson,
and
D.J.Mangelsdorf
(2003).
The Drosophila orphan nuclear receptor DHR38 mediates an atypical ecdysteroid signaling pathway.
|
| |
Cell,
113,
731-742.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
M.Färnegårdh,
T.Bonn,
S.Sun,
J.Ljunggren,
H.Ahola,
A.Wilhelmsson,
J.A.Gustafsson,
and
M.Carlquist
(2003).
The three-dimensional structure of the liver X receptor beta reveals a flexible ligand-binding pocket that can accommodate fundamentally different ligands.
|
| |
J Biol Chem,
278,
38821-38828.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
M.Gianní,
A.Tarrade,
E.A.Nigro,
E.Garattini,
and
C.Rochette-Egly
(2003).
The AF-1 and AF-2 domains of RAR gamma 2 and RXR alpha cooperate for triggering the transactivation and the degradation of RAR gamma 2/RXR alpha heterodimers.
|
| |
J Biol Chem,
278,
34458-34466.
|
|
|
|
|
|
|
M.Schapira,
B.M.Raaka,
S.Das,
L.Fan,
M.Totrov,
Z.Zhou,
S.R.Wilson,
R.Abagyan,
and
H.H.Samuels
(2003).
Discovery of diverse thyroid hormone receptor antagonists by high-throughput docking.
|
| |
Proc Natl Acad Sci U S A,
100,
7354-7359.
|
|
|
|
|
|
|
P.J.Martin,
M.H.Delmotte,
P.Formstecher,
and
P.Lefebvre
(2003).
PLZF is a negative regulator of retinoic acid receptor transcriptional activity.
|
| |
Nucl Recept,
1,
6.
|
|
|
|
|
|
|
R.Hertz,
N.Ben-Haim,
A.D.Petrescu,
B.Kalderon,
I.Berman,
N.Eldad,
F.Schroeder,
and
J.Bar-Tana
(2003).
Rescue of MODY-1 by agonist ligands of hepatocyte nuclear factor-4alpha.
|
| |
J Biol Chem,
278,
22578-22585.
|
|
|
|
|
|
|
S.Benko,
J.D.Love,
M.Beládi,
J.W.Schwabe,
and
L.Nagy
(2003).
Molecular determinants of the balance between co-repressor and co-activator recruitment to the retinoic acid receptor.
|
| |
J Biol Chem,
278,
43797-43806.
|
|
|
|
|
|
|
S.Yamada,
M.Shimizu,
and
K.Yamamoto
(2003).
Structure-function relationships of vitamin D including ligand recognition by the vitamin D receptor.
|
| |
Med Res Rev,
23,
89.
|
|
|
|
|
|
|
V.Vivat-Hannah,
W.Bourguet,
M.Gottardis,
and
H.Gronemeyer
(2003).
Separation of retinoid X receptor homo- and heterodimerization functions.
|
| |
Mol Cell Biol,
23,
7678-7688.
|
|
|
|
|
|
|
A.K.Shiau,
D.Barstad,
J.T.Radek,
M.J.Meyers,
K.W.Nettles,
B.S.Katzenellenbogen,
J.A.Katzenellenbogen,
D.A.Agard,
and
G.L.Greene
(2002).
Structural characterization of a subtype-selective ligand reveals a novel mode of estrogen receptor antagonism.
|
| |
Nat Struct Biol,
9,
359-364.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
A.Keriel,
A.Stary,
A.Sarasin,
C.Rochette-Egly,
and
J.M.Egly
(2002).
XPD mutations prevent TFIIH-dependent transactivation by nuclear receptors and phosphorylation of RARalpha.
|
| |
Cell,
109,
125-135.
|
|
|
|
|
|
|
B.Lefebvre,
K.Ozato,
and
P.Lefebvre
(2002).
Phosphorylation of histone H3 is functionally linked to retinoic acid receptor beta promoter activation.
|
| |
EMBO Rep,
3,
335-340.
|
|
|
|
|
|
|
F.C.Zusi,
M.V.Lorenzi,
and
V.Vivat-Hannah
(2002).
Selective retinoids and rexinoids in cancer therapy and chemoprevention.
|
| |
Drug Discov Today,
7,
1165-1174.
|
|
|
|
|
|
|
G.B.Wisely,
A.B.Miller,
R.G.Davis,
A.D.Thornquest,
R.Johnson,
T.Spitzer,
A.Sefler,
B.Shearer,
J.T.Moore,
A.B.Miller,
T.M.Willson,
and
S.P.Williams
(2002).
Hepatocyte nuclear factor 4 is a transcription factor that constitutively binds fatty acids.
|
| |
Structure,
10,
1225-1234.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
H.Greschik,
J.M.Wurtz,
S.Sanglier,
W.Bourguet,
A.van Dorsselaer,
D.Moras,
and
J.P.Renaud
(2002).
Structural and functional evidence for ligand-independent transcriptional activation by the estrogen-related receptor 3.
|
| |
Mol Cell,
9,
303-313.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
J.C.Ghosh,
X.Yang,
A.Zhang,
M.H.Lambert,
H.Li,
H.E.Xu,
and
J.D.Chen
(2002).
Interactions that determine the assembly of a retinoid X receptor/corepressor complex.
|
| |
Proc Natl Acad Sci U S A,
99,
5842-5847.
|
|
|
|
|
|
|
J.D.Love,
J.T.Gooch,
S.Benko,
C.Li,
L.Nagy,
V.K.Chatterjee,
R.M.Evans,
and
J.W.Schwabe
(2002).
The structural basis for the specificity of retinoid-X receptor-selective agonists: new insights into the role of helix H12.
|
| |
J Biol Chem,
277,
11385-11391.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
M.Benkoussa,
C.Brand,
M.H.Delmotte,
P.Formstecher,
and
P.Lefebvre
(2002).
Retinoic acid receptors inhibit AP1 activation by regulating extracellular signal-regulated kinase and CBP recruitment to an AP1-responsive promoter.
|
| |
Mol Cell Biol,
22,
4522-4534.
|
|
|
|
|
|
|
M.Desclozeaux,
I.N.Krylova,
F.Horn,
R.J.Fletterick,
and
H.A.Ingraham
(2002).
Phosphorylation and intramolecular stabilization of the ligand binding domain in the nuclear receptor steroidogenic factor 1.
|
| |
Mol Cell Biol,
22,
7193-7203.
|
|
|
|
|
|
|
P.Aarnisalo,
C.H.Kim,
J.W.Lee,
and
T.Perlmann
(2002).
Defining requirements for heterodimerization between the retinoid X receptor and the orphan nuclear receptor Nurr1.
|
| |
J Biol Chem,
277,
35118-35123.
|
|
|
|
|
|
|
P.Sacchetti,
H.Dwornik,
P.Formstecher,
C.Rachez,
and
P.Lefebvre
(2002).
Requirements for heterodimerization between the orphan nuclear receptor Nurr1 and retinoid X receptors.
|
| |
J Biol Chem,
277,
35088-35096.
|
|
|
|
|
|
|
S.Dhe-Paganon,
K.Duda,
M.Iwamoto,
Y.I.Chi,
and
S.E.Shoelson
(2002).
Crystal structure of the HNF4 alpha ligand binding domain in complex with endogenous fatty acid ligand.
|
| |
J Biol Chem,
277,
37973-37976.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
S.H.McLaughlin,
and
S.E.Jackson
(2002).
Folding and stability of the ligand-binding domain of the glucocorticoid receptor.
|
| |
Protein Sci,
11,
1926-1936.
|
|
|
|
|
|
|
A.C.Steinmetz,
J.P.Renaud,
and
D.Moras
(2001).
Binding of ligands and activation of transcription by nuclear receptors.
|
| |
Annu Rev Biophys Biomol Struct,
30,
329-359.
|
|
|
|
|
|
|
C.Stehlin,
J.M.Wurtz,
A.Steinmetz,
E.Greiner,
R.Schüle,
D.Moras,
and
J.P.Renaud
(2001).
X-ray structure of the orphan nuclear receptor RORbeta ligand-binding domain in the active conformation.
|
| |
EMBO J,
20,
5822-5831.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
D.L.Osburn,
G.Shao,
H.M.Seidel,
and
I.G.Schulman
(2001).
Ligand-dependent degradation of retinoid X receptors does not require transcriptional activity or coactivator interactions.
|
| |
Mol Cell Biol,
21,
4909-4918.
|
|
|
|
|
|
|
G.M.Clayton,
S.Y.Peak-Chew,
R.M.Evans,
and
J.W.Schwabe
(2001).
The structure of the ultraspiracle ligand-binding domain reveals a nuclear receptor locked in an inactive conformation.
|
| |
Proc Natl Acad Sci U S A,
98,
1549-1554.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
I.Zelko,
T.Sueyoshi,
T.Kawamoto,
R.Moore,
and
M.Negishi
(2001).
The peptide near the C terminus regulates receptor CAR nuclear translocation induced by xenochemicals in mouse liver.
|
| |
Mol Cell Biol,
21,
2838-2846.
|
|
|
|
|
|
|
J.O.Boyle
(2001).
Retinoid mechanisms and cyclins.
|
| |
Curr Oncol Rep,
3,
301-305.
|
|
|
|
|
|
|
S.Khorasanizadeh,
and
F.Rastinejad
(2001).
Nuclear-receptor interactions on DNA-response elements.
|
| |
Trends Biochem Sci,
26,
384-390.
|
|
|
|
|
|
|
X.Hu,
Y.Li,
and
M.A.Lazar
(2001).
Determinants of CoRNR-dependent repression complex assembly on nuclear hormone receptors.
|
| |
Mol Cell Biol,
21,
1747-1758.
|
|
|
|
|
|
|
A.M.de Urquiza,
S.Liu,
M.Sjöberg,
R.H.Zetterström,
W.Griffiths,
J.Sjövall,
and
T.Perlmann
(2000).
Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain.
|
| |
Science,
290,
2140-2144.
|
|
|
|
|
|
|
B.P.Klaholz,
and
D.Moras
(2000).
Structural role of a detergent molecule in retinoic acid nuclear receptor crystals.
|
| |
Acta Crystallogr D Biol Crystallogr,
56,
933-935.
|
|
|
|
|
|
|
D.S.Geller,
A.Farhi,
N.Pinkerton,
M.Fradley,
M.Moritz,
A.Spitzer,
G.Meinke,
F.T.Tsai,
P.B.Sigler,
and
R.P.Lifton
(2000).
Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy.
|
| |
Science,
289,
119-123.
|
|
|
|
|
|
|
P.F.Egea,
A.Mitschler,
N.Rochel,
M.Ruff,
P.Chambon,
and
D.Moras
(2000).
Crystal structure of the human RXRalpha ligand-binding domain bound to its natural ligand: 9-cis retinoic acid.
|
| |
EMBO J,
19,
2592-2601.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
R.T.Gampe,
V.G.Montana,
M.H.Lambert,
A.B.Miller,
R.K.Bledsoe,
M.V.Milburn,
S.A.Kliewer,
T.M.Willson,
and
H.E.Xu
(2000).
Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors.
|
| |
Mol Cell,
5,
545-555.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
R.T.Gampe,
V.G.Montana,
M.H.Lambert,
G.B.Wisely,
M.V.Milburn,
and
H.E.Xu
(2000).
Structural basis for autorepression of retinoid X receptor by tetramer formation and the AF-2 helix.
|
| |
Genes Dev,
14,
2229-2241.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
W.Bourguet,
P.Germain,
and
H.Gronemeyer
(2000).
Nuclear receptor ligand-binding domains: three-dimensional structures, molecular interactions and pharmacological implications.
|
| |
Trends Pharmacol Sci,
21,
381-388.
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