3ZEH: Solution structure of the Hs. PSIP1 PWWP domain

BACKGROUND: Recognition of histone modifications by specialized protein domains is a key step in the regulation of DNA-mediated processes like gene transcription. The structural basis of these interactions is usually studied using histone peptide models, neglecting the nucleosomal context. Here, we provide the structural and thermodynamic basis for the recognition of H3K36-methylated (H3K36me) nucleosomes by the PSIP1-PWWP domain, based on extensive mutational analysis, advanced nuclear magnetic resonance (NMR), and computational approaches. RESULTS: The PSIP1-PWWP domain binds H3K36me3 peptide and DNA with low affinity, through distinct, adjacent binding surfaces. PWWP binding to H3K36me nucleosomes is enhanced approximately 10,000-fold compared to a methylated peptide. Based on mutational analyses and NMR data, we derive a structure of the complex showing that the PWWP domain is bound to H3K36me nucleosomes through simultaneous interactions with both methylated histone tail and nucleosomal DNA. CONCLUSION: Concerted binding to the methylated histone tail and nucleosomal DNA underlies the high- affinity, specific recognition of H3K36me nucleosomes by the PSIP1-PWWP domain. We propose that this bipartite binding mechanism is a distinctive and general property in the recognition of histone modifications close to the nucleosome core.
PDB ID: 3ZEHDownload
MMDB ID: 110218
PDB Deposition Date: 2012/12/5
Updated in MMDB: 2018/05
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Biological Unit for 3ZEH: monomeric; determined by author and by software (PQS)
Molecular Components in 3ZEH
Label Count Molecule
Protein (1 molecule)
PC4 and Sfrs1-interacting Protein(Gene symbol: PSIP1)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB