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Distinct conformational states of nuclear receptor-bound CRSP-Med complexes

Dylan J Taatjes1, Tilman Schneider-Poetsch, Robert Tjian

  • 1Howard Hughes Medical Institute, Department of Molecular and Cell Biology, 401 Barker Hall, University of California, Berkeley, California 94720, USA.

Nature Structural & Molecular Biology
|June 15, 2004
PubMed

Insights

The CRSP-Med coactivator complex changes shape when bound by different proteins. Nuclear receptors like thyroid hormone receptor (TR) and vitamin D receptor (VDR) induce a shared structural shift primarily by moving the Med220 subunit.

Area of Science:

  • Molecular biology
  • Structural biology
  • Biochemistry

Background:

  • The CRSP-Med coactivator complex interacts with various regulatory proteins.
  • Previous studies revealed distinct conformational changes upon binding of VP16 and SREBP-1a activators.

Purpose of the Study:

  • To investigate the structural basis of CRSP-Med conformational changes induced by nuclear receptors.
  • To determine if nuclear receptors binding to the same subunit induce similar structural alterations.

Main Methods:

  • Electron microscopy (EM) and single-particle reconstruction techniques were employed.
  • Structural analysis of CRSP-Med complexed with thyroid hormone receptor (TR) and vitamin D receptor (VDR).

Main Results:

  • TR and VDR binding to CRSP-Med induced a shared conformational feature distinct from other known structures.
  • This nuclear receptor-induced shift is largely dependent on the movement of the Med220 subunit.
  • Resolution of the analyzed complexes was 29 Å.

Conclusions:

  • The Med220 subunit plays a key role in mediating conformational changes in the CRSP-Med complex.
  • Nuclear receptors targeting the same subunit induce a conserved structural response.
  • Understanding these structural dynamics is crucial for coactivator function regulation.

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