4jxt
CID of human RPRD1A in complex with a phosphorylated peptide from RPB1-CTD
Structural highlights
FunctionRPR1A_HUMAN Interacts with phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit POLR2A, and participates in dephosphorylation of the CTD. May act as a negative regulator of cyclin-D1 (CCND1) and cyclin-E (CCNE1) in the cell cycle.[1] [2] Publication Abstract from PubMedThe RNA polymerase II (RNAPII) C-terminal domain (CTD) heptapeptide repeats (1-YSPTSPS-7) undergo dynamic phosphorylation and dephosphorylation during the transcription cycle to recruit factors that regulate transcription, RNA processing and chromatin modification. We show here that RPRD1A and RPRD1B form homodimers and heterodimers through their coiled-coil domains and interact preferentially via CTD-interaction domains (CIDs) with RNAPII CTD repeats phosphorylated at S2 and S7. Crystal structures of the RPRD1A, RPRD1B and RPRD2 CIDs, alone and in complex with RNAPII CTD phosphoisoforms, elucidate the molecular basis of CTD recognition. In an example of cross-talk between different CTD modifications, our data also indicate that RPRD1A and RPRD1B associate directly with RPAP2 phosphatase and, by interacting with CTD repeats where phospho-S2 and/or phospho-S7 bracket a phospho-S5 residue, serve as CTD scaffolds to coordinate the dephosphorylation of phospho-S5 by RPAP2. RPRD1A and RPRD1B are human RNA polymerase II C-terminal domain scaffolds for Ser5 dephosphorylation.,Ni Z, Xu C, Guo X, Hunter GO, Kuznetsova OV, Tempel W, Marcon E, Zhong G, Guo H, Kuo WH, Li J, Young P, Olsen JB, Wan C, Loppnau P, El Bakkouri M, Senisterra GA, He H, Huang H, Sidhu SS, Emili A, Murphy S, Mosley AL, Arrowsmith CH, Min J, Greenblatt JF Nat Struct Mol Biol. 2014 Jul 6. doi: 10.1038/nsmb.2853. PMID:24997600[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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