CTD-specific phosphatase Scp1 in complex with peptide C-terminal domain of RNA polymerase IICTD-specific phosphatase Scp1 in complex with peptide C-terminal domain of RNA polymerase II

Structural highlights

2ghq is a 4 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 2.05Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CTDS1_HUMAN Preferentially catalyzes the dephosphorylation of 'Ser-5' within the tandem 7 residues repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A. Negatively regulates RNA polymerase II transcription, possibly by controlling the transition from initiation/capping to processive transcript elongation. Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells.[1] [2]

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

Phosphorylation and dephosphorylation of the C-terminal domain (CTD) of RNA polymerase II (Pol II) represent a critical regulatory checkpoint for transcription. Transcription initiation requires Fcp1/Scp1-mediated dephosphorylation of phospho-CTD. Fcp1 and Scp1 belong to a family of Mg2+ -dependent phosphoserine (P.Ser)/phosphothreonine (P.Thr)-specific phosphatases. We recently showed that Scp1 is an evolutionarily conserved regulator of neuronal gene silencing. Here, we present the X-ray crystal structures of a dominant-negative form of human Scp1 (D96N mutant) bound to mono- and diphosphorylated peptides encompassing the CTD heptad repeat (Y1S2P3T4S5P6S7). Moreover, kinetic and thermodynamic analyses of Scp1-phospho-CTD peptide complexes support the structures determined. This combined structure-function analysis discloses the residues in Scp1 involved in CTD binding and its preferential dephosphorylation of P.Ser5 of the CTD heptad repeat. Moreover, these results provide a template for the design of specific inhibitors of Scp1 for the study of neuronal stem cell development.

Determinants for dephosphorylation of the RNA polymerase II C-terminal domain by Scp1.,Zhang Y, Kim Y, Genoud N, Gao J, Kelly JW, Pfaff SL, Gill GN, Dixon JE, Noel JP Mol Cell. 2006 Dec 8;24(5):759-70. PMID:17157258[3]

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

See Also

References

  1. Yeo M, Lin PS, Dahmus ME, Gill GN. A novel RNA polymerase II C-terminal domain phosphatase that preferentially dephosphorylates serine 5. J Biol Chem. 2003 Jul 11;278(28):26078-85. Epub 2003 Apr 28. PMID:12721286 doi:10.1074/jbc.M301791200
  2. Yeo M, Lee SK, Lee B, Ruiz EC, Pfaff SL, Gill GN. Small CTD phosphatases function in silencing neuronal gene expression. Science. 2005 Jan 28;307(5709):596-600. PMID:15681389 doi:10.1126/science.1100801
  3. Zhang Y, Kim Y, Genoud N, Gao J, Kelly JW, Pfaff SL, Gill GN, Dixon JE, Noel JP. Determinants for dephosphorylation of the RNA polymerase II C-terminal domain by Scp1. Mol Cell. 2006 Dec 8;24(5):759-70. PMID:17157258 doi:10.1016/j.molcel.2006.10.027

2ghq, resolution 2.05Å

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