Nuclear receptor corepressor

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Structure of human nuclear receptor corepressor 2 SMRT (magenta, cyan) complex with retinoic acid receptor LBD (grey, green, pink, yellow) and the antagonistic ligand Rhein (PDB entry 3r2a)

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Function

Nuclear receptor corepressors (N-CoR) and SMRT (Silencing Mediator of Retinoic acid and Thyroid hormone receptor) mediate the repression of gene subscription by nuclear receptors^[1]. N-CoRs contain interaction domains with a conserved LXXII hydrophobic motif. This motif resembles the LXXLL motif of nuclear receptors^[2].

Nuclear receptor corepressor 1 plays a role in repressing cardiac hypertrophy^[3].
Nuclear receptor corepressor 2 is part of a multisubunit complex which modify chromatin structure.

Relevance

N-CoR1 may play an important role in human cancers^[4]. SMRT has a role in mitochondrial oxidative metabolism and the aging process^[5].

Structural highlights

The LXXII motif of the SMRT corepressor binds to the ligand binding domain of the retinoid acid repressor. The antagonist ligand Rhein binds to cysteine residue in the hydrophobic pocket of the repressor^[6].

↑ Xu HE, Stanley TB, Montana VG, Lambert MH, Shearer BG, Cobb JE, McKee DD, Galardi CM, Plunket KD, Nolte RT, Parks DJ, Moore JT, Kliewer SA, Willson TM, Stimmel JB. Structural basis for antagonist-mediated recruitment of nuclear co-repressors by PPARalpha. Nature. 2002 Feb 14;415(6873):813-7. PMID:11845213 doi:10.1038/415813a
↑ Webb P, Anderson CM, Valentine C, Nguyen P, Marimuthu A, West BL, Baxter JD, Kushner PJ. The nuclear receptor corepressor (N-CoR) contains three isoleucine motifs (I/LXXII) that serve as receptor interaction domains (IDs). Mol Endocrinol. 2000 Dec;14(12):1976-85. doi: 10.1210/mend.14.12.0566. PMID:11117528 doi:https://dx.doi.org/10.1210/mend.14.12.0566
↑ Li C, Sun XN, Chen BY, Zeng MR, Du LJ, Liu T, Gu HH, Liu Y, Li YL, Zhou LJ, Zheng XJ, Zhang YY, Zhang WC, Liu Y, Shi C, Shao S, Shi XR, Yi Y, Liu X, Wang J, Auwerx J, Wang ZV, Jia F, Li RG, Duan SZ. Nuclear receptor corepressor 1 represses cardiac hypertrophy. EMBO Mol Med. 2019 Nov 7;11(11):e9127. PMID:31532577 doi:10.15252/emmm.201809127
↑ Fozzatti L, Park JW, Zhao L, Willingham MC, Cheng SY. Oncogenic Actions of the Nuclear Receptor Corepressor (NCOR1) in a Mouse Model of Thyroid Cancer. PLoS One. 2013 Jun 26;8(6):e67954. doi: 10.1371/journal.pone.0067954. Print 2013. PMID:23840792 doi:https://dx.doi.org/10.1371/journal.pone.0067954
↑ Reilly SM, Bhargava P, Liu S, Gangl MR, Gorgun C, Nofsinger RR, Evans RM, Qi L, Hu FB, Lee CH. Nuclear receptor corepressor SMRT regulates mitochondrial oxidative metabolism and mediates aging-related metabolic deterioration. Cell Metab. 2010 Dec 1;12(6):643-53. doi: 10.1016/j.cmet.2010.11.007. PMID:21109196 doi:https://dx.doi.org/10.1016/j.cmet.2010.11.007
↑ Zhang H, Chen L, Chen J, Jiang H, Shen X. Structural basis for retinoic X receptor repression on the tetramer. J Biol Chem. 2011 May 24. PMID:21613212 doi:10.1074/jbc.M111.245498

3D Structures of nuclear receptor corepressor

Updated on 17-July-2024

References

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Joel L. Sussman

[1] Xu HE, Stanley TB, Montana VG, Lambert MH, Shearer BG, Cobb JE, McKee DD, Galardi CM, Plunket KD, Nolte RT, Parks DJ, Moore JT, Kliewer SA, Willson TM, Stimmel JB. Structural basis for antagonist-mediated recruitment of nuclear co-repressors by PPARalpha. Nature. 2002 Feb 14;415(6873):813-7. PMID:11845213 doi:10.1038/415813a

[2] Webb P, Anderson CM, Valentine C, Nguyen P, Marimuthu A, West BL, Baxter JD, Kushner PJ. The nuclear receptor corepressor (N-CoR) contains three isoleucine motifs (I/LXXII) that serve as receptor interaction domains (IDs). Mol Endocrinol. 2000 Dec;14(12):1976-85. doi: 10.1210/mend.14.12.0566. PMID:11117528 doi:https://dx.doi.org/10.1210/mend.14.12.0566

[3] Li C, Sun XN, Chen BY, Zeng MR, Du LJ, Liu T, Gu HH, Liu Y, Li YL, Zhou LJ, Zheng XJ, Zhang YY, Zhang WC, Liu Y, Shi C, Shao S, Shi XR, Yi Y, Liu X, Wang J, Auwerx J, Wang ZV, Jia F, Li RG, Duan SZ. Nuclear receptor corepressor 1 represses cardiac hypertrophy. EMBO Mol Med. 2019 Nov 7;11(11):e9127. PMID:31532577 doi:10.15252/emmm.201809127

[4] Fozzatti L, Park JW, Zhao L, Willingham MC, Cheng SY. Oncogenic Actions of the Nuclear Receptor Corepressor (NCOR1) in a Mouse Model of Thyroid Cancer. PLoS One. 2013 Jun 26;8(6):e67954. doi: 10.1371/journal.pone.0067954. Print 2013. PMID:23840792 doi:https://dx.doi.org/10.1371/journal.pone.0067954

[5] Reilly SM, Bhargava P, Liu S, Gangl MR, Gorgun C, Nofsinger RR, Evans RM, Qi L, Hu FB, Lee CH. Nuclear receptor corepressor SMRT regulates mitochondrial oxidative metabolism and mediates aging-related metabolic deterioration. Cell Metab. 2010 Dec 1;12(6):643-53. doi: 10.1016/j.cmet.2010.11.007. PMID:21109196 doi:https://dx.doi.org/10.1016/j.cmet.2010.11.007

[6] Zhang H, Chen L, Chen J, Jiang H, Shen X. Structural basis for retinoic X receptor repression on the tetramer. J Biol Chem. 2011 May 24. PMID:21613212 doi:10.1074/jbc.M111.245498

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Nuclear receptor corepressor

Function

Relevance

Structural highlights

3D Structures of nuclear receptor corepressor

References

Proteopedia Page Contributors and Editors (what is this?)

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