2GHT

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

Summary for 2GHT

• Entry DOI: 10.2210/pdb2ght/pdb
• Related: 1ta0 2GHQ
• Descriptor: Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1, DNA-directed RNA polymerase II largest subunit, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: protein-peptide complex, had superfamily, hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q9GZU7 P24928
• Total number of polymer chains: 4
• Total formula weight: 43611.74

Authors

Zhang, Y.,Noel, J.P. (deposition date: 2006-03-27, release date: 2006-12-05, Last modification date: 2024-10-30)

Primary citation

Zhang, Y.,Kim, Y.,Genoud, N.,Gao, J.,Kelly, J.W.,Pfaff, S.L.,Gill, G.N.,Dixon, J.E.,Noel, J.P.
Determinants for dephosphorylation of the RNA polymerase II C-terminal domain by Scp1.
Mol.Cell, 24:759-770, 2006

PubMed Abstract: 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.

PubMed: 17157258
DOI: 10.1016/j.molcel.2006.10.027

Experimental method

X-RAY DIFFRACTION (1.8 Å)