6npw

SSu72/Sympk in complex with Ser2/Ser5 phosphorylated peptideSSu72/Sympk in complex with Ser2/Ser5 phosphorylated peptide

Structural highlights 6npw is a 5 chain structure with sequence from Drosophila melanogaster and Saccharomyces cerevisiae RM11-1a. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.486Å 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. Publication Abstract from PubMed The C-terminal domain of RNA polymerase II (CTD) contains a repetitive heptad sequence (YSPTSPS) whose phosphorylation states coordinate eukaryotic transcription by recruiting protein regulators. The precise placement and removal of phosphate groups on specific residues of the CTD are critical for the fidelity and effectiveness of RNA polymerase II-mediated transcription. During transcriptional elongation, phosphoryl-Ser5 (pSer5) is gradually dephosphorylated by CTD phosphatases, while Ser2 phosphorylation is accumulating. Using MS, X-ray crystallography, protein engineering, and immunoblotting analyses, here we investigated the structure and function of SSU72 homolog, RNA polymerase II CTD phosphatase (Ssu72, from Drosophila melanogaster), an essential CTD phosphatase that dephosphorylates pSer5 at the transition from elongation to termination, to determine the mechanism by which Ssu72 distinguishes the highly similar pSer2 and pSer5 CTDs. We found that Ssu72 dephosphorylates pSer5 effectively, but only has low activities toward pSer7 and pSer2. The structural analysis revealed that Ssu72 requires that the proline residue in the substrate's SP motif is in the cis configuration, forming a tight beta-turn for recognition by Ssu72. We also noted that residues flanking the SP motif, such as the bulky Tyr1 next to Ser2, prevent the formation of such configuration and enable Ssu72 to distinguish among the different SP motifs. The phosphorylation of Tyr-1 further prohibited Ssu72 binding to pSer2 and thereby prevented untimely Ser2 dephosphorylation. Our results reveal critical roles for Tyr1 in differentiating the phosphorylation states of Ser2/Ser5 of CTD in RNA polymerase II, which occur at different stages of transcription. Structural determinants for accurate dephosphorylation of RNA polymerase II by its cognate CTD phosphatase during eukaryotic transcription.,Irani S, Sipe SN, Yang W, Burkholder NT, Lin B, Sim K, Matthews WL, Brodbelt JS, Zhang Y J Biol Chem. 2019 Apr 10. pii: RA119.007697. doi: 10.1074/jbc.RA119.007697. PMID:30971428 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Symplekin

spinqualitylabelsall models 6npw, resolution 2.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image