PMID- 32974652
OWN - NLM
STAT- MEDLINE
DCOM- 20201109
LR  - 20201109
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 48
IP  - 17
DP  - 2020 Sep 25
TI  - Structural basis for DNA recognition and allosteric control of the retinoic acid 
      receptors RAR-RXR.
PG  - 9969-9985
LID - 10.1093/nar/gkaa697 [doi]
AB  - Retinoic acid receptors (RARs) as a functional heterodimer with retinoid X 
      receptors (RXRs), bind a diverse series of RA-response elements (RAREs) in 
      regulated genes. Among them, the non-canonical DR0 elements are bound by RXR-RAR 
      with comparable affinities to DR5 elements but DR0 elements do not act 
      transcriptionally as independent RAREs. In this work, we present structural 
      insights for the recognition of DR5 and DR0 elements by RXR-RAR heterodimer using 
      x-ray crystallography, small angle x-ray scattering, and hydrogen/deuterium 
      exchange coupled to mass spectrometry. We solved the crystal structures of 
      RXR-RAR DNA-binding domain in complex with the Rarb2 DR5 and RXR-RXR DNA-binding 
      domain in complex with Hoxb13 DR0. While cooperative binding was observed on DR5, 
      the two molecules bound non-cooperatively on DR0 on opposite sides of the DNA. In 
      addition, our data unveil the structural organization and dynamics of the 
      multi-domain RXR-RAR DNA complexes providing evidence for DNA-dependent 
      allosteric communication between domains. Differential binding modes between DR0 
      and DR5 were observed leading to differences in conformation and structural 
      dynamics of the multi-domain RXR-RAR DNA complexes. These results reveal that the 
      topological organization of the RAR binding element confer regulatory information 
      by modulating the overall topology and structural dynamics of the RXR-RAR 
      heterodimers.
CI  - (c) The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic 
      Acids Research.
FAU - Osz, Judit
AU  - Osz J
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Illkirch, 
      France.
AD  - Institut National de La Sante et de La Recherche Medicale (INSERM) U1258, 
      Illkirch, France.
AD  - Centre National de Recherche Scientifique (CNRS) UMR 7104, Illkirch, France.
AD  - Universite de Strasbourg, Illkirch, France.
FAU - McEwen, Alastair G
AU  - McEwen AG
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Illkirch, 
      France.
AD  - Institut National de La Sante et de La Recherche Medicale (INSERM) U1258, 
      Illkirch, France.
AD  - Centre National de Recherche Scientifique (CNRS) UMR 7104, Illkirch, France.
AD  - Universite de Strasbourg, Illkirch, France.
FAU - Bourguet, Maxime
AU  - Bourguet M
AD  - Laboratoire de Spectrometrie de Masse BioOrganique, Universite de Strasbourg, 
      CNRS UMR 7178, IPHC, Strasbourg, France.
FAU - Przybilla, Frederic
AU  - Przybilla F
AD  - Laboratoire de Bioimagerie et Pathologies, CNRS UMR 7021, Faculte de Pharmacie, 
      Universite de Strasbourg, Illkirch, France.
FAU - Peluso-Iltis, Carole
AU  - Peluso-Iltis C
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Illkirch, 
      France.
AD  - Institut National de La Sante et de La Recherche Medicale (INSERM) U1258, 
      Illkirch, France.
AD  - Centre National de Recherche Scientifique (CNRS) UMR 7104, Illkirch, France.
AD  - Universite de Strasbourg, Illkirch, France.
FAU - Poussin-Courmontagne, Pierre
AU  - Poussin-Courmontagne P
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Illkirch, 
      France.
AD  - Institut National de La Sante et de La Recherche Medicale (INSERM) U1258, 
      Illkirch, France.
AD  - Centre National de Recherche Scientifique (CNRS) UMR 7104, Illkirch, France.
AD  - Universite de Strasbourg, Illkirch, France.
FAU - Mely, Yves
AU  - Mely Y
AD  - Laboratoire de Bioimagerie et Pathologies, CNRS UMR 7021, Faculte de Pharmacie, 
      Universite de Strasbourg, Illkirch, France.
FAU - Cianferani, Sarah
AU  - Cianferani S
AD  - Laboratoire de Spectrometrie de Masse BioOrganique, Universite de Strasbourg, 
      CNRS UMR 7178, IPHC, Strasbourg, France.
FAU - Jeffries, Cy M
AU  - Jeffries CM
AD  - European Molecular Biology Laboratory, Hamburg Outstation, Hamburg, Germany.
FAU - Svergun, Dmitri I
AU  - Svergun DI
AD  - European Molecular Biology Laboratory, Hamburg Outstation, Hamburg, Germany.
FAU - Rochel, Natacha
AU  - Rochel N
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Illkirch, 
      France.
AD  - Institut National de La Sante et de La Recherche Medicale (INSERM) U1258, 
      Illkirch, France.
AD  - Centre National de Recherche Scientifique (CNRS) UMR 7104, Illkirch, France.
AD  - Universite de Strasbourg, Illkirch, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (HOXB13 protein, human)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Allosteric Regulation
MH  - *Allosteric Site
MH  - DNA/chemistry/metabolism
MH  - Homeodomain Proteins/genetics
MH  - Humans
MH  - Molecular Docking Simulation
MH  - Protein Binding
MH  - *Response Elements
MH  - Retinoid X Receptors/*chemistry/metabolism
PMC - PMC7515732
EDAT- 2020/09/26 06:00
MHDA- 2020/11/11 06:00
PMCR- 2020/08/25
CRDT- 2020/09/25 06:05
PHST- 2020/08/12 00:00 [accepted]
PHST- 2020/07/16 00:00 [revised]
PHST- 2020/03/28 00:00 [received]
PHST- 2020/09/25 06:05 [entrez]
PHST- 2020/09/26 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
PHST- 2020/08/25 00:00 [pmc-release]
AID - 5896908 [pii]
AID - gkaa697 [pii]
AID - 10.1093/nar/gkaa697 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2020 Sep 25;48(17):9969-9985. doi: 10.1093/nar/gkaa697.