4ygx

Crystal Structure of D. melanogaster Ssu72+Symplekin bound to cis peptidomimetic CTD phospho-Ser5 peptideCrystal Structure of D. melanogaster Ssu72+Symplekin bound to cis peptidomimetic CTD phospho-Ser5 peptide

Structural highlights

4ygx is a 5 chain structure with sequence from Drosophila melanogaster and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.95Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SYMPK_DROME Component of a protein complex required for cotranscriptional processing of 3'-ends of polyadenylated and histone pre-mRNA.^[1] ^[2]

Publication Abstract from PubMed

Proline isomerization greatly impacts biological signaling but is subtle and difficult to detect in proteins. We characterize this poorly understood regulatory mechanism for RNA polymerase II carboxyl terminal domain (CTD) phosphorylation state using novel, direct, and quantitative chemical tools. We determine the proline isomeric preference of three CTD phosphatases: Ssu72 as cis-proline specific, Scp1 and Fcp1 as strongly trans-preferred. Due to this inherent characteristic, these phosphatases respond differently to enzymes that catalyze the isomerization of proline, like Ess1/Pin1. We demonstrate that this selective regulation of RNA polymerase II phosphorylation state exists within human cells, consistent with in vitro assays. These results support a model in which, instead of a global enhancement of downstream enzymatic activities, proline isomerases selectively boost the activity of a subset of CTD regulatory factors specific for cis-proline. This leads to diversified phosphorylation states of CTD in vitro and in cells. We provide the chemical tools to investigate proline isomerization and its ability to selectively enhance signaling in transcription and other biological contexts.

Chemical Tools To Decipher Regulation of Phosphatases by Proline Isomerization on Eukaryotic RNA Polymerase II.,Mayfield JE, Fan S, Wei S, Zhang M, Li B, Ellington AD, Etzkorn FA, Zhang YJ ACS Chem Biol. 2015 Sep 15. PMID:26332362^[3]

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

References

↑ Wagner EJ, Burch BD, Godfrey AC, Salzler HR, Duronio RJ, Marzluff WF. A genome-wide RNA interference screen reveals that variant histones are necessary for replication-dependent histone pre-mRNA processing. Mol Cell. 2007 Nov 30;28(4):692-9. PMID:18042462 doi:10.1016/j.molcel.2007.10.009
↑ Sullivan KD, Steiniger M, Marzluff WF. A core complex of CPSF73, CPSF100, and Symplekin may form two different cleavage factors for processing of poly(A) and histone mRNAs. Mol Cell. 2009 May 15;34(3):322-32. doi: 10.1016/j.molcel.2009.04.024. PMID:19450530 doi:10.1016/j.molcel.2009.04.024
↑ Mayfield JE, Fan S, Wei S, Zhang M, Li B, Ellington AD, Etzkorn FA, Zhang YJ. Chemical Tools To Decipher Regulation of Phosphatases by Proline Isomerization on Eukaryotic RNA Polymerase II. ACS Chem Biol. 2015 Sep 15. PMID:26332362 doi:http://dx.doi.org/10.1021/acschembio.5b00296

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OCA

[1] Wagner EJ, Burch BD, Godfrey AC, Salzler HR, Duronio RJ, Marzluff WF. A genome-wide RNA interference screen reveals that variant histones are necessary for replication-dependent histone pre-mRNA processing. Mol Cell. 2007 Nov 30;28(4):692-9. PMID:18042462 doi:10.1016/j.molcel.2007.10.009

[2] Sullivan KD, Steiniger M, Marzluff WF. A core complex of CPSF73, CPSF100, and Symplekin may form two different cleavage factors for processing of poly(A) and histone mRNAs. Mol Cell. 2009 May 15;34(3):322-32. doi: 10.1016/j.molcel.2009.04.024. PMID:19450530 doi:10.1016/j.molcel.2009.04.024

[3] Mayfield JE, Fan S, Wei S, Zhang M, Li B, Ellington AD, Etzkorn FA, Zhang YJ. Chemical Tools To Decipher Regulation of Phosphatases by Proline Isomerization on Eukaryotic RNA Polymerase II. ACS Chem Biol. 2015 Sep 15. PMID:26332362 doi:http://dx.doi.org/10.1021/acschembio.5b00296

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