PMID- 23995840
OWN - NLM
STAT- MEDLINE
DCOM- 20131231
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 288
IP  - 42
DP  - 2013 Oct 18
TI  - Regulation of the structurally dynamic N-terminal domain of progesterone receptor 
      by protein-induced folding.
PG  - 30285-30299
LID - S0021-9258(20)85702-0 [pii]
LID - 10.1074/jbc.M113.491787 [doi]
AB  - The N-terminal domain (NTD) of steroid receptors harbors a transcriptional 
      activation function (AF1) that is composed of an intrinsically disordered 
      polypeptide. We examined the interaction of the TATA-binding protein (TBP) with 
      the NTD of the progesterone receptor (PR) and its ability to regulate AF1 
      activity through coupled folding and binding. As assessed by solution phase 
      biophysical methods, the isolated NTD of PR contains a large content of random 
      coil, and it is capable of adopting secondary alpha-helical structure and more stable 
      tertiary folding either in the presence of the natural osmolyte 
      trimethylamine-N-oxide or through a direct interaction with TBP. 
      Hydrogen-deuterium exchange coupled with mass spectrometry confirmed the highly 
      dynamic intrinsically disordered property of the NTD within the context of 
      full-length PR. Deletion mapping and point mutagenesis defined a region of the 
      NTD (amino acids 350-428) required for structural folding in response to TBP 
      interaction. Overexpression of TBP in cells enhanced transcriptional activity 
      mediated by the PR NTD, and deletion mutations showed that a region (amino acids 
      327-428), similar to that required for TBP-induced folding, was required for 
      functional response. TBP also increased steroid receptor co-activator 1 (SRC-1) 
      interaction with the PR NTD and cooperated with SRC-1 to stimulate NTD-dependent 
      transcriptional activity. These data suggest that TBP can mediate structural 
      reorganization of the NTD to facilitate the binding of co-activators required for 
      maximal transcriptional activation.
FAU - Kumar, Raj
AU  - Kumar R
AD  - the Department of Basic Sciences, Commonwealth Medical College, Scranton, 
      Pennsylvania 18509.
FAU - Moure, Carmen M
AU  - Moure CM
AD  - From the Departments of Molecular and Cellular Biology and.
FAU - Khan, Shagufta H
AU  - Khan SH
AD  - the Department of Basic Sciences, Commonwealth Medical College, Scranton, 
      Pennsylvania 18509.
FAU - Callaway, Celetta
AU  - Callaway C
AD  - From the Departments of Molecular and Cellular Biology and.
FAU - Grimm, Sandra L
AU  - Grimm SL
AD  - From the Departments of Molecular and Cellular Biology and.
FAU - Goswami, Devrishi
AU  - Goswami D
AD  - the Department of Molecular Therapeutics, The Scripps Research Institute, 
      Jupiter, Florida 33458, and.
FAU - Griffin, Patrick R
AU  - Griffin PR
AD  - the Department of Molecular Therapeutics, The Scripps Research Institute, 
      Jupiter, Florida 33458, and.
FAU - Edwards, Dean P
AU  - Edwards DP
AD  - From the Departments of Molecular and Cellular Biology and; Pathology and 
      Immunology, Baylor College of Medicine, Houston, Texas 77030,. Electronic 
      address: deane@bcm.edu.
LA  - eng
GR  - R01CA046938/CA/NCI NIH HHS/United States
GR  - U54 MH084512/MH/NIMH NIH HHS/United States
GR  - GM084041/GM/NIGMS NIH HHS/United States
GR  - P30 CA125123/CA/NCI NIH HHS/United States
GR  - R01 GM084041/GM/NIGMS NIH HHS/United States
GR  - S10 RR027270/RR/NCRR NIH HHS/United States
GR  - P30 NCI-CA125123/CA/NCI NIH HHS/United States
GR  - R01 CA046938/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130830
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Receptors, Progesterone)
RN  - 0 (TATA-Box Binding Protein)
RN  - 0 (TBP protein, human)
RN  - EC 2.3.1.48 (NCOA1 protein, human)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - Humans
MH  - Nuclear Receptor Coactivator 1/chemistry/genetics/*metabolism
MH  - Point Mutation
MH  - *Protein Folding
MH  - Protein Structure, Secondary
MH  - Protein Structure, Tertiary
MH  - Receptors, Progesterone/chemistry/genetics/*metabolism
MH  - Sequence Deletion
MH  - TATA-Box Binding Protein/chemistry/genetics/*metabolism
MH  - Transcriptional Activation/*physiology
PMC - PMC3798494
OTO - NOTNLM
OT  - Hydrogen Deuterium Exchange Mass
OT  - Intrinsically Disordered Proteins
OT  - Mass Spectrometry (MS)
OT  - N-terminal Transcription Activation domain AF1
OT  - Progesterone
OT  - Progesterone Receptor
OT  - Protein Folding
OT  - Steroid Hormone Receptor
OT  - TATA-binding Protein
EDAT- 2013/09/03 06:00
MHDA- 2014/01/01 06:00
PMCR- 2014/10/18
CRDT- 2013/09/03 06:00
PHST- 2013/09/03 06:00 [entrez]
PHST- 2013/09/03 06:00 [pubmed]
PHST- 2014/01/01 06:00 [medline]
PHST- 2014/10/18 00:00 [pmc-release]
AID - S0021-9258(20)85702-0 [pii]
AID - M113.491787 [pii]
AID - 10.1074/jbc.M113.491787 [doi]
PST - ppublish
SO  - J Biol Chem. 2013 Oct 18;288(42):30285-30299. doi: 10.1074/jbc.M113.491787. Epub 
      2013 Aug 30.