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Structure paper

TitleMolecular basis of histone tail recognition by human TIP5 PHD finger and bromodomain of the chromatin remodeling complex NoRC.
Journal, issue, pagesStructure, Vol. 23, Issue 1, Page 80-92, Year 2015
Publish dateJan 6, 2015
AuthorsCynthia Tallant / Erica Valentini / Oleg Fedorov / Lois Overvoorde / Fleur M Ferguson / Panagis Filippakopoulos / Dmitri I Svergun / Stefan Knapp / Alessio Ciulli /
PubMed AbstractBinding of the chromatin remodeling complex NoRC to RNA complementary to the rDNA promoter mediates transcriptional repression. TIP5, the largest subunit of NoRC, is involved in recruitment to rDNA ...Binding of the chromatin remodeling complex NoRC to RNA complementary to the rDNA promoter mediates transcriptional repression. TIP5, the largest subunit of NoRC, is involved in recruitment to rDNA by interactions with promoter-bound TTF-I, pRNA, and acetylation of H4K16. TIP5 domains that recognize posttranslational modifications on histones are essential for recruitment of NoRC to chromatin, but how these reader modules recognize site-specific histone tails has remained elusive. Here, we report crystal structures of PHD zinc finger and bromodomains from human TIP5 and BAZ2B in free form and bound to H3 and/or H4 histones. PHD finger functions as an independent structural module in recognizing unmodified H3 histone tails, and the bromodomain prefers H3 and H4 acetylation marks followed by a key basic residue, KacXXR. Further low-resolution analyses of PHD-bromodomain modules provide molecular insights into their trans histone tail recognition, required for nucleosome recruitment and transcriptional repression of the NoRC complex.
External linksStructure / PubMed:25533489 / PubMed Central
MethodsSAS (X-ray synchrotron) / X-ray diffraction
Resolution1.6 - 1.99 Å
Structure data

SASDA46:
TIP5 in Tris (Bromodomain adjacent to zinc finger domain protein 2A, TIP5)
Method: SAXS/SANS

SASDA56:
BAZ2B in Tris (Bromodomain adjacent to zinc finger domain protein 2B, C-terminal, BAZ2B)
Method: SAXS/SANS

SASDA66: BAZ2B-18mer complex in Tris (Bromodomain adjacent to zinc finger domain protein 2B, C-terminal, BAZ2B + H3Kac9Kac14, peptide 18mer)
Method: SAXS/SANS

PDB-4lz2:
Crystal structure of the bromodomain of human BAZ2A
Method: X-RAY DIFFRACTION / Resolution: 1.76 Å

PDB-4q6f:
Crystal structure of human BAZ2A PHD zinc finger in complex with unmodified H3K4 histone peptide
Method: X-RAY DIFFRACTION / Resolution: 1.91 Å

PDB-4qbm:
Crystal structure of human BAZ2A bromodomain in complex with a diacetylated histone 4 peptide (H4K16acK20ac)
Method: X-RAY DIFFRACTION / Resolution: 1.65 Å

PDB-4qc1:
Crystal structure of human BAZ2B bromodomain in complex with an acetylated histone 3 peptide (H3K14ac)
Method: X-RAY DIFFRACTION / Resolution: 1.99 Å

PDB-4qc3:
Crystal structure of human BAZ2B bromodomain in complex with a diacetylated histone 4 peptide (H4K8acK12ac)
Method: X-RAY DIFFRACTION / Resolution: 1.6 Å

PDB-4qf2:
Crystal structure of human BAZ2A PHD zinc finger in the free form
Method: X-RAY DIFFRACTION / Resolution: 1.7 Å

PDB-4qf3:
Crystal structure of human BAZ2B PHD zinc finger in the free form
Method: X-RAY DIFFRACTION / Resolution: 1.6 Å

Chemicals

ChemComp-EDO:
1,2-ETHANEDIOL

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER

ChemComp-ZN:
Unknown entry

ChemComp-SO4:
SULFATE ION

ChemComp-PO4:
PHOSPHATE ION

ChemComp-GOL:
GLYCEROL

Source
  • homo sapiens (human)
KeywordsSIGNALING PROTEIN / Structural Genomics Consortium / SGC / TRANSCRIPTION / Bromodomain adjacent to zinc finger domain protein 2A / Transcription termination factor I-interacting protein 5 / TTF-I-interacting protein 5 / Tip5 / Bromodomain / Bromodomain adjacent to zinc finger domain protein 2B / hWALp4 / KIAA1476 / transcriptional regulation / transcriptional regulation interacting with ISWI

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