Format

Send to:

Choose Destination
See comment in PubMed Commons below
Genes Dev. 1998 Nov 1;12(21):3343-56.

Structure and specificity of nuclear receptor-coactivator interactions.

Author information

  • 1Department of Cellular and Molecular Pharmacology, University of California at San Francisco (UCSF), San Francisco, California 94143 USA.

Abstract

Combinatorial regulation of transcription implies flexible yet precise assembly of multiprotein regulatory complexes in response to signals. Biochemical and crystallographic analyses revealed that hormone binding leads to the formation of a hydrophobic groove within the ligand binding domain (LBD) of the thyroid hormone receptor that interacts with an LxxLL motif-containing alpha-helix from GRIP1, a coactivator. Residues immediately adjacent to the motif modulate the affinity of the interaction; the motif and the adjacent sequences are employed to different extents in binding to different receptors. Such interactions of amphipathic alpha-helices with hydrophobic grooves define protein interfaces in other regulatory complexes as well. We suggest that these common structural elements impart flexibility to combinatorial regulation, whereas side chains at the interface impart specificity.

PMID:
9808622
[PubMed - indexed for MEDLINE]
PMCID:
PMC317236
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk