3U5O: Crystal Structure Of The Complex Of Trim33 Phd-Bromo And H3(1-22) K9me3k14ack18ac Histone Peptide

Citation:
Abstract
Specific chromatin marks keep master regulators of differentiation silent yet poised for activation by extracellular signals. We report that nodal TGF-beta signals use the poised histone mark H3K9me3 to trigger differentiation of mammalian embryonic stem cells. Nodal receptors induce the formation of companion Smad4-Smad2/3 and TRIM33-Smad2/3 complexes. The PHD-Bromo cassette of TRIM33 facilitates binding of TRIM33-Smad2/3 to H3K9me3 and H3K18ac on the promoters of mesendoderm regulators Gsc and Mixl1. The crystal structure of this cassette, bound to histone H3 peptides, illustrates that PHD recognizes K9me3, and Bromo binds an adjacent K18ac. The interaction between TRIM33-Smad2/3 and H3K9me3 displaces the chromatin-compacting factor HP1gamma, making nodal response elements accessible to Smad4-Smad2/3 for Pol II recruitment. In turn, Smad4 increases K18 acetylation to augment TRIM33-Smad2/3 binding. Thus, nodal effectors use the H3K9me3 mark as a platform to switch master regulators of stem cell differentiation from the poised to the active state.
PDB ID: 3U5ODownload
MMDB ID: 96548
PDB Deposition Date: 2011/10/11
Updated in MMDB: 2012/01
Experimental Method:
x-ray diffraction
Resolution: 2.7  Å
Source Organism:
Similar Structures:
Biological Unit for 3U5O: dimeric; determined by author and by software (PISA)
Molecular Components in 3U5O
Label Count Molecule
Proteins (2 molecules)
1
E3 Ubiquitin-protein Ligase Trim33(Gene symbol: TRIM33)
Molecule annotation
1
Histone H3.1(Gene symbol: HIST1H3A)
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.