PMID- 10207113
OWN - NLM
STAT- MEDLINE
DCOM- 19990518
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 5
DP  - 1999 May
TI  - Molecular determinants of the estrogen receptor-coactivator interface.
PG  - 3895-903
AB  - Transcriptional activation by the estrogen receptor is mediated through its
      interaction with coactivator proteins upon ligand binding. By systematic
      mutagenesis, we have identified a group of conserved hydrophobic residues in the 
      ligand binding domain that are required for binding the p160 family of
      coactivators. Together with helix 12 and lysine 366 at the C-terminal end of
      helix 3, they form a hydrophobic groove that accommodates an LXXLL motif, which
      is essential for mediating coactivator binding to the receptor. Furthermore, we
      demonstrated that the high-affinity binding of motif 2, conserved in the p160
      family, is due to the presence of three basic residues N terminal to the core
      LXXLL motif. The recruitment of p160 coactivators to the estrogen receptor is
      therefore likely to depend not only on the LXXLL motif making hydrophobic
      interactions with the docking surface on the receptor, but also on adjacent basic
      residues, which may be involved in the recognition of charged residues on the
      receptor to allow the initial docking of the motif.
FAU - Mak, H Y
AU  - Mak HY
AD  - Molecular Endocrinology Laboratory, Imperial Cancer Research Fund, London WC2A
      3PX, United Kingdom.
FAU - Hoare, S
AU  - Hoare S
FAU - Henttu, P M
AU  - Henttu PM
FAU - Parker, M G
AU  - Parker MG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Ligands)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Transcription Factors)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding, Competitive
MH  - COS Cells
MH  - DNA-Binding Proteins/analysis
MH  - Estradiol/metabolism
MH  - Histone Acetyltransferases
MH  - *Ligands
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Mutagenesis/genetics
MH  - Mutation/genetics
MH  - Nuclear Receptor Coactivator 1
MH  - Peptide Fragments/chemistry/pharmacology
MH  - Protein Binding
MH  - Protein Structure, Secondary
MH  - Receptors, Estrogen/*chemistry/genetics
MH  - Sequence Alignment
MH  - Transcription Factors/*metabolism
MH  - Transfection
PMC - PMC84247
EDAT- 1999/04/17 00:00
MHDA- 1999/04/17 00:01
CRDT- 1999/04/17 00:00
PHST- 1999/04/17 00:00 [pubmed]
PHST- 1999/04/17 00:01 [medline]
PHST- 1999/04/17 00:00 [entrez]
AID - 10.1128/mcb.19.5.3895 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 May;19(5):3895-903. doi: 10.1128/mcb.19.5.3895.