PMID- 21049972
OWN - NLM
STAT- MEDLINE
DCOM- 20121127
LR  - 20230106
IS  - 1520-4995 (Electronic)
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 50
IP  - 1
DP  - 2011 Jan 11
TI  - Structure, energetics, and dynamics of binding coactivator peptide to the human 
      retinoid X receptor alpha ligand binding domain complex with 9-cis-retinoic acid.
PG  - 93-105
AB  - Retinoid X receptors (RXRs) are ligand-dependent nuclear receptors, which are 
      activated by the potent agonist 9-cis-retinoic acid (9cRA). 9cRA binds to the 
      ligand binding domain (LBD) of RXRs and recruits coactivator proteins for gene 
      transcription. Using isothermal titration calorimetry, the binding of a 13-mer 
      coactivator peptide, GRIP-1, to the hRXRalpha-LBD homodimer complex containing 9cRA 
      (hRXRalpha-LBD:9cRA:GRIP-1) is reported between 20 and 37  degrees C. DeltaG is temperature 
      independent (-8.5 kcal/mol), and GRIP-1 binding is driven by DeltaH (-9.2 kcal/mol) 
      at 25  degrees C. DeltaC(p) is large and negative (-401 cal mol(-1) K(-1)). The crystal 
      structure of hRXRalpha-LBD:9cRA:GRIP-1 is reported at 2.05 A. When the structures of 
      hRXRalpha-LBD:9cRA:GRIP-1 and hRXRalpha-LBD:9cRA ( 1FBY ) homodimers are compared, E453 
      and E456 on helix 12 bury and form ionic interactions with GRIP-1. R302 on helix 
      4 realigns to form new salt bridges to both E453 and E456. F277 (helix 3), F437 
      (helix 11), and F450 (helix 12) move toward the hydrophobic interior. The changes 
      in the near-UV spectrum at 260 nm of the hRXRalpha-LBD:9cRA:GRIP-1 support this 
      structural change. Helix 11 tilts toward helix 12 by  approximately 1 A, modifying the ring 
      conformation of 9cRA. Hydrogen-deuterium exchange mass spectroscopy indicates 
      GRIP-1 binding to hRXRalpha-LBD:9cRA significantly decreases the exchange rates for 
      peptides containing helices 3 (F277), 4 (R302), 11 (F437), and 12 (E453, E456). 
      The structural changes and loss of dynamics of the GRIP-1-bound structure are 
      used to interpret the energetics of coactivator peptide binding to the 
      agonist-bound hRXRalpha-LBD.
FAU - Xia, Gang
AU  - Xia G
AD  - Department of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama 
      35294, United States.
FAU - Boerma, LeeAnn J
AU  - Boerma LJ
FAU - Cox, Bryan D
AU  - Cox BD
FAU - Qiu, Cheng
AU  - Qiu C
FAU - Kang, Sebyung
AU  - Kang S
FAU - Smith, Craig D
AU  - Smith CD
FAU - Renfrow, Matthew B
AU  - Renfrow MB
FAU - Muccio, Donald D
AU  - Muccio DD
LA  - eng
SI  - PDB/3OAP
GR  - RR17261/RR/NCRR NIH HHS/United States
GR  - P50 CA089019/CA/NCI NIH HHS/United States
GR  - 2 P50 CA089019/CA/NCI NIH HHS/United States
GR  - S10 RR017261/RR/NCRR NIH HHS/United States
GR  - 5 P50CA089019/CA/NCI NIH HHS/United States
GR  - P50 CA089019-09/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101208
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Ligands)
RN  - 0 (Nuclear Receptor Coactivator 2)
RN  - 0 (Retinoid X Receptor alpha)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Alitretinoin
MH  - Amino Acid Sequence
MH  - Crystallography, X-Ray
MH  - Humans
MH  - Ligands
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Nuclear Receptor Coactivator 2/chemistry/*metabolism
MH  - Protein Binding
MH  - Protein Multimerization
MH  - Protein Structure, Tertiary
MH  - Retinoid X Receptor alpha/chemistry/*metabolism
MH  - Spectrophotometry, Ultraviolet
MH  - Thermodynamics
MH  - Tretinoin/chemistry/*metabolism
PMC - PMC3081989
MID - NIHMS257563
EDAT- 2010/11/06 06:00
MHDA- 2012/12/10 06:00
PMCR- 2012/06/08
CRDT- 2010/11/06 06:00
PHST- 2010/11/06 06:00 [entrez]
PHST- 2010/11/06 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2012/06/08 00:00 [pmc-release]
AID - 10.1021/bi101288y [doi]
PST - ppublish
SO  - Biochemistry. 2011 Jan 11;50(1):93-105. doi: 10.1021/bi101288y. Epub 2010 Dec 8.