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3o2s

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Revision as of 21:15, 25 December 2014

Crystal structure of the human symplekin-Ssu72 complex

Structural highlights

3o2s is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3o2q, 3o2t
Gene:	SYMPK, SPK (Homo sapiens), SSU72, HSPC182, PNAS-120 (Homo sapiens)
Activity:	Phosphoprotein phosphatase, with EC number 3.1.3.16
Resources:	FirstGlance, OCA, RCSB, PDBsum

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] [SSU72_HUMAN] Protein phosphatase that catalyzes the dephosphorylation of the C-terminal domain of RNA polymerase II. Plays a role in RNA processing and termination. Plays a role in pre-mRNA polyadenylation via its interaction with SYMPK.^[3] ^[4] ^[5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Symplekin (Pta1 in yeast) is a scaffold in the large protein complex that is required for 3'-end cleavage and polyadenylation of eukaryotic messenger RNA precursors (pre-mRNAs); it also participates in transcription initiation and termination by RNA polymerase II (Pol II). Symplekin mediates interactions between many different proteins in this machinery, although the molecular basis for its function is not known. Here we report the crystal structure at 2.4 A resolution of the amino-terminal domain (residues 30-340) of human symplekin in a ternary complex with the Pol II carboxy-terminal domain (CTD) Ser 5 phosphatase Ssu72 (refs 7, 10-17) and a CTD Ser 5 phosphopeptide. The N-terminal domain of symplekin has the ARM or HEAT fold, with seven pairs of antiparallel alpha-helices arranged in the shape of an arc. The structure of Ssu72 has some similarity to that of low-molecular-mass phosphotyrosine protein phosphatase, although Ssu72 has a unique active-site landscape as well as extra structural features at the C terminus that are important for interaction with symplekin. Ssu72 is bound to the concave face of symplekin, and engineered mutations in this interface can abolish interactions between the two proteins. The CTD peptide is bound in the active site of Ssu72, with the pSer 5-Pro 6 peptide bond in the cis configuration, which contrasts with all other known CTD peptide conformations. Although the active site of Ssu72 is about 25 A from the interface with symplekin, we found that the symplekin N-terminal domain stimulates Ssu72 CTD phosphatase activity in vitro. Furthermore, the N-terminal domain of symplekin inhibits polyadenylation in vitro, but only when coupled to transcription. Because catalytically active Ssu72 overcomes this inhibition, our results show a role for mammalian Ssu72 in transcription-coupled pre-mRNA 3'-end processing.

Crystal structure of the human symplekin-Ssu72-CTD phosphopeptide complex.,Xiang K, Nagaike T, Xiang S, Kilic T, Beh MM, Manley JL, Tong L Nature. 2010 Sep 22. PMID:20861839^[6]

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
↑ St-Pierre B, Liu X, Kha LC, Zhu X, Ryan O, Jiang Z, Zacksenhaus E. Conserved and specific functions of mammalian ssu72. Nucleic Acids Res. 2005 Jan 19;33(2):464-77. Print 2005. PMID:15659578 doi:http://dx.doi.org/33/2/464
↑ 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
↑ 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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3o2s"

@@ Line 9: / Line 9: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3o2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o2s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3o2s RCSB], [http://www.ebi.ac.uk/pdbsum/3o2s PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/SYMPK_HUMAN 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.<ref>PMID:16230528</ref> <ref>PMID:20861839</ref>  [[http://www.uniprot.org/uniprot/SSU72_HUMAN SSU72_HUMAN]] Protein phosphatase that catalyzes the dephosphorylation of the C-terminal domain of RNA polymerase II. Plays a role in RNA processing and termination. Plays a role in pre-mRNA polyadenylation via its interaction with SYMPK.<ref>PMID:15659578</ref> <ref>PMID:20861839</ref> <ref>PMID:23070812</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

3o2s

From Proteopedia

Revision as of 21:15, 25 December 2014

Crystal structure of the human symplekin-Ssu72 complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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