PMID- 33647291
OWN - NLM
STAT- MEDLINE
DCOM- 20210625
LR  - 20210625
IS  - 1089-8638 (Electronic)
IS  - 0022-2836 (Linking)
VI  - 433
IP  - 9
DP  - 2021 Apr 30
TI  - Structural Insights into the Interaction of the Intrinsically Disordered 
      Co-activator TIF2 with Retinoic Acid Receptor Heterodimer (RXR/RAR).
PG  - 166899
LID - S0022-2836(21)00093-0 [pii]
LID - 10.1016/j.jmb.2021.166899 [doi]
AB  - Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) form heterodimers 
      that activate target gene transcription by recruiting co-activator complexes in 
      response to ligand binding. The nuclear receptor (NR) co-activator TIF2 mediates 
      this recruitment by interacting with the ligand-binding domain (LBD) of NRs 
      trough the nuclear receptor interaction domain (TIF2(NRID)) containing three 
      highly conserved alpha-helical LxxLL motifs (NR-boxes). The precise binding mode of 
      this domain to RXR/RAR is not clear due to the disordered nature of TIF2. Here we 
      present the structural characterization of TIF2(NRID) by integrating several 
      experimental (NMR, SAXS, Far-UV CD, SEC-MALS) and computational data. 
      Collectively, the data are in agreement with a largely disordered protein with 
      partially structured regions, including the NR-boxes and their flanking regions, 
      which are evolutionary conserved. NMR and X-ray crystallographic data on 
      TIF2(NRID) in complex with RXR/RAR reveal a multisite binding of the three 
      NR-boxes as well as an active role of their flanking regions in the interaction.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Senicourt, Lucile
AU  - Senicourt L
AD  - Centre de Biochimie Structurale (CBS), CNRS, INSERM, Univ Montpellier, 
      Montpellier, France.
FAU - le Maire, Albane
AU  - le Maire A
AD  - Centre de Biochimie Structurale (CBS), CNRS, INSERM, Univ Montpellier, 
      Montpellier, France.
FAU - Allemand, Frederic
AU  - Allemand F
AD  - Centre de Biochimie Structurale (CBS), CNRS, INSERM, Univ Montpellier, 
      Montpellier, France.
FAU - Carvalho, JoAo E
AU  - Carvalho JE
AD  - Institute for Research on Cancer and Aging (IRCAN), INSERM U1081 - CNRS UMR 7284, 
      Universite Cote d'Azur, 28, Avenue de Valombrose, 06107 Nice, France.
FAU - Guee, Laura
AU  - Guee L
AD  - Centre de Biochimie Structurale (CBS), CNRS, INSERM, Univ Montpellier, 
      Montpellier, France.
FAU - Germain, Pierre
AU  - Germain P
AD  - Centre de Biochimie Structurale (CBS), CNRS, INSERM, Univ Montpellier, 
      Montpellier, France.
FAU - Schubert, Michael
AU  - Schubert M
AD  - Evolution of Intercellular Signaling in Development (EvoInSiDe), UMR 7009 - 
      CNRS/Sorbonne Universite), Institut de la Mer de Villefranche, 181 Chemin du 
      Lazaret, 06230 Villefranche-sur-Mer, France.
FAU - Bernado, Pau
AU  - Bernado P
AD  - Centre de Biochimie Structurale (CBS), CNRS, INSERM, Univ Montpellier, 
      Montpellier, France.
FAU - Bourguet, William
AU  - Bourguet W
AD  - Centre de Biochimie Structurale (CBS), CNRS, INSERM, Univ Montpellier, 
      Montpellier, France. Electronic address: william.bourguet@cbs.cnrs.fr.
FAU - Sibille, Nathalie
AU  - Sibille N
AD  - Centre de Biochimie Structurale (CBS), CNRS, INSERM, Univ Montpellier, 
      Montpellier, France. Electronic address: nathalie.sibille@cbs.cnrs.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210227
PL  - Netherlands
TA  - J Mol Biol
JT  - Journal of molecular biology
JID - 2985088R
RN  - 0 (Intrinsically Disordered Proteins)
RN  - 0 (Ligands)
RN  - 0 (NCOA2 protein, human)
RN  - 0 (Nuclear Receptor Coactivator 2)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Crystallography, X-Ray
MH  - Fluorescence Polarization
MH  - Humans
MH  - Intrinsically Disordered Proteins/chemistry/metabolism
MH  - Ligands
MH  - Mice
MH  - Models, Molecular
MH  - Nuclear Magnetic Resonance, Biomolecular
MH  - Nuclear Receptor Coactivator 2/*chemistry/*metabolism
MH  - Protein Binding
MH  - Protein Multimerization
MH  - Protein Structure, Secondary
MH  - Receptors, Retinoic Acid/*chemistry/*metabolism
MH  - Retinoid X Receptors/*chemistry/*metabolism
OTO - NOTNLM
OT  - NMR
OT  - X-ray crystallography
OT  - co-activator protein
OT  - intrinsically disordered protein
OT  - nuclear hormone receptors
EDAT- 2021/03/02 06:00
MHDA- 2021/06/29 06:00
CRDT- 2021/03/01 20:11
PHST- 2020/11/02 00:00 [received]
PHST- 2021/02/02 00:00 [revised]
PHST- 2021/02/22 00:00 [accepted]
PHST- 2021/03/02 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2021/03/01 20:11 [entrez]
AID - S0022-2836(21)00093-0 [pii]
AID - 10.1016/j.jmb.2021.166899 [doi]
PST - ppublish
SO  - J Mol Biol. 2021 Apr 30;433(9):166899. doi: 10.1016/j.jmb.2021.166899. Epub 2021 
      Feb 27.