4b6h
From Proteopedia
Structure of hDcp1a in complex with proline rich sequence of PNRC2
Structural highlights
Function[DCP1A_HUMAN] Necessary for the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay. Removes the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP. Contributes to the transactivation of target genes after stimulation by TGFB1.[1] [2] [PNRC2_HUMAN] Involved in nonsense-mediated mRNA decay (NMD) by acting as a bridge between the mRNA decapping complex and the NMD machinery. May act by targeting the NMD machinery to the P-body and recruiting the decapping machinery to aberrant mRNAs. Required for UPF1/RENT1 localization to the P-body. Also acts as a nuclear receptor coactivator. May play a role in controlling the energy balance between energy storage and energy expenditure.[3] [4] Publication Abstract from PubMedNonsense-mediated mRNA decay (NMD) is an important mRNA surveillance system, and human PNRC2 protein mediates the link between mRNA surveillance and decapping. However, the mechanism by which PNRC2 interacts with the mRNA surveillance machinery and stimulates NMD is unknown. Here, we present the crystal structure of Dcp1a in complex with PNRC2. The proline-rich region of PNRC2 is bound to the EVH1 domain of Dcp1a, while its NR-box mediates the interaction with the hyperphosphorylated Upf1. The mode of PNRC2 interaction with Dcp1a is distinct from those observed in other EVH1/proline-rich ligands interactions. Disruption of the interaction of PNRC2 with Dcp1a abolishes its P-body localization and ability to promote mRNA degradation when tethered to mRNAs. PNRC2 acts in synergy with Dcp1a to stimulate the decapping activity of Dcp2 by bridging the interaction between Dcp1a and Dcp2, suggesting that PNRC2 is a decapping coactivator in addition to its adaptor role in NMD. Structural basis of the PNRC2-mediated link between mrna surveillance and decapping.,Lai T, Cho H, Liu Z, Bowler MW, Piao S, Parker R, Kim YK, Song H Structure. 2012 Dec 5;20(12):2025-37. doi: 10.1016/j.str.2012.09.009. Epub 2012, Oct 18. PMID:23085078[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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