PMID- 11222743
OWN - NLM
STAT- MEDLINE
DCOM- 20010510
LR  - 20131121
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 15
IP  - 3
DP  - 2001 Mar
TI  - Probing conformational changes in the estrogen receptor: evidence for a partially 
      unfolded intermediate facilitating ligand binding and release.
PG  - 421-8
AB  - Because the ligand bound to the ligand-binding domain (LBD) of nuclear hormone 
      receptors is completely enveloped by protein, it is thought that the process of 
      ligand binding or unbinding must involve a significant conformational change of 
      this domain. We have used the intrinsic tryptophan fluorescence of the estrogen 
      receptor-alpha (ERalpha) or estrogen receptor-beta (ERbeta) LBD, as well as 
      bis-anilinonaphthalenesulfonate (bis-ANS), a probe for accessible interior 
      regions of protein, to follow the guanidine-hydrochloride (Gua-HCl)-induced 
      unfolding of this domain. In both cases, we find that the ER-LBD unfolding 
      follows a two-phase process. At low Gua-HCl, the ER-LBD undergoes partial 
      unfolding, whereas at high Gua-HCl, this domain undergoes a global unfolding, 
      with bis-ANS binding preferentially to the partially unfolded state. The 
      partially unfolded state of the ERalpha-LBD induced by denaturant does not bind 
      ligand stably, but it may resemble an intermediate that this domain accesses 
      transiently under native conditions that allow ligands to enter or exit the 
      ligand-binding pocket.
FAU - Gee, A C
AU  - Gee AC
AD  - Department of Chemistry University of Illinois Urbana, Illinois 61801, USA.
FAU - Katzenellenbogen, J A
AU  - Katzenellenbogen JA
LA  - eng
GR  - 1R37 DK-15556/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Anilino Naphthalenesulfonates)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Receptors, Estrogen)
RN  - 63741-13-9 (5,5'-bis(8-(phenylamino)-1-naphthalenesulfonate))
RN  - 8DUH1N11BX (Tryptophan)
RN  - JU58VJ6Y3B (Guanidine)
SB  - IM
MH  - Anilino Naphthalenesulfonates/chemistry
MH  - Binding Sites
MH  - Estrogen Receptor alpha
MH  - Fluorescence
MH  - Fluorescent Dyes/chemistry
MH  - Guanidine/chemistry
MH  - Humans
MH  - Protein Conformation
MH  - Protein Denaturation
MH  - *Protein Folding
MH  - Receptors, Estrogen/*chemistry/*metabolism
MH  - Spectrometry, Fluorescence
MH  - Tryptophan/chemistry
EDAT- 2001/02/27 10:00
MHDA- 2001/05/22 10:01
CRDT- 2001/02/27 10:00
PHST- 2001/02/27 10:00 [pubmed]
PHST- 2001/05/22 10:01 [medline]
PHST- 2001/02/27 10:00 [entrez]
AID - 10.1210/mend.15.3.0602 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2001 Mar;15(3):421-8. doi: 10.1210/mend.15.3.0602.