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4h3h

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Crystal structure of a ternary complex of human symplekin NTD, human Ssu72 and a RNA poymerase II CTD peptide phosphorylated at SER-7

Structural highlights

4h3h is a 5 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.2Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SYMPK_HUMAN Scaffold protein that functions as a component of a multimolecular complex involved in histone mRNA 3'-end processing. Specific component of the tight junction (TJ) plaque, but might not be an exclusively junctional component. May have a house-keeping rule. Is involved in pre-mRNA polyadenylation. Enhances SSU72 phosphatase activity.^[1] ^[2]

Publication Abstract from PubMed

Ssu72, an RNA polymerase II C-terminal domain (CTD) phospho-Ser5 (pSer5) phosphatase, was recently reported to have pSer7 phosphatase activity as well. We report here the crystal structure of a ternary complex of the N-terminal domain of human symplekin, human Ssu72, and a 10-mer pSer7 CTD peptide. Surprisingly, the peptide is bound in the Ssu72 active site with its backbone running in the opposite direction compared with a pSer5 peptide. The pSer7 phosphatase activity of Ssu72 is approximately 4000-fold lower than its pSer5 phosphatase activity toward a peptide substrate, consistent with the structural observations.

An unexpected binding mode for a Pol II CTD peptide phosphorylated at Ser7 in the active site of the CTD phosphatase Ssu72.,Xiang K, Manley JL, Tong L Genes Dev. 2012 Oct 15;26(20):2265-70. doi: 10.1101/gad.198853.112. PMID:23070812^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kolev NG, Steitz JA. Symplekin and multiple other polyadenylation factors participate in 3'-end maturation of histone mRNAs. Genes Dev. 2005 Nov 1;19(21):2583-92. Epub 2005 Oct 17. PMID:16230528 doi:10.1101/gad.1371105
↑ Xiang K, Nagaike T, Xiang S, Kilic T, Beh MM, Manley JL, Tong L. Crystal structure of the human symplekin-Ssu72-CTD phosphopeptide complex. Nature. 2010 Sep 22. PMID:20861839 doi:10.1038/nature09391
↑ Xiang K, Manley JL, Tong L. An unexpected binding mode for a Pol II CTD peptide phosphorylated at Ser7 in the active site of the CTD phosphatase Ssu72. Genes Dev. 2012 Oct 15;26(20):2265-70. doi: 10.1101/gad.198853.112. PMID:23070812 doi:http://dx.doi.org/10.1101/gad.198853.112