4b6h | pdb_00004b6h

Structure of hDcp1a in complex with proline rich sequence of PNRC2

Structural highlights

4b6h is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 PubMed

Nonsense-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

↑ Bai RY, Koester C, Ouyang T, Hahn SA, Hammerschmidt M, Peschel C, Duyster J. SMIF, a Smad4-interacting protein that functions as a co-activator in TGFbeta signalling. Nat Cell Biol. 2002 Mar;4(3):181-90. PMID:11836524 doi:https://dx.doi.org/10.1038/ncb753
↑ Lykke-Andersen J. Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay. Mol Cell Biol. 2002 Dec;22(23):8114-21. PMID:12417715
↑ Zhou D, Chen S. PNRC2 is a 16 kDa coactivator that interacts with nuclear receptors through an SH3-binding motif. Nucleic Acids Res. 2001 Oct 1;29(19):3939-48. PMID:11574675
↑ Cho H, Kim KM, Kim YK. Human proline-rich nuclear receptor coregulatory protein 2 mediates an interaction between mRNA surveillance machinery and decapping complex. Mol Cell. 2009 Jan 16;33(1):75-86. doi: 10.1016/j.molcel.2008.11.022. PMID:19150429 doi:https://dx.doi.org/10.1016/j.molcel.2008.11.022
↑ Lai T, Cho H, Liu Z, Bowler MW, Piao S, Parker R, Kim YK, Song H. Structural basis of the PNRC2-mediated link between mrna surveillance and decapping. Structure. 2012 Dec 5;20(12):2025-37. doi: 10.1016/j.str.2012.09.009. Epub 2012, Oct 18. PMID:23085078 doi:https://dx.doi.org/10.1016/j.str.2012.09.009

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OCA

[1] Bai RY, Koester C, Ouyang T, Hahn SA, Hammerschmidt M, Peschel C, Duyster J. SMIF, a Smad4-interacting protein that functions as a co-activator in TGFbeta signalling. Nat Cell Biol. 2002 Mar;4(3):181-90. PMID:11836524 doi:https://dx.doi.org/10.1038/ncb753

[2] Lykke-Andersen J. Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay. Mol Cell Biol. 2002 Dec;22(23):8114-21. PMID:12417715

[3] Zhou D, Chen S. PNRC2 is a 16 kDa coactivator that interacts with nuclear receptors through an SH3-binding motif. Nucleic Acids Res. 2001 Oct 1;29(19):3939-48. PMID:11574675

[4] Cho H, Kim KM, Kim YK. Human proline-rich nuclear receptor coregulatory protein 2 mediates an interaction between mRNA surveillance machinery and decapping complex. Mol Cell. 2009 Jan 16;33(1):75-86. doi: 10.1016/j.molcel.2008.11.022. PMID:19150429 doi:https://dx.doi.org/10.1016/j.molcel.2008.11.022

[5] Lai T, Cho H, Liu Z, Bowler MW, Piao S, Parker R, Kim YK, Song H. Structural basis of the PNRC2-mediated link between mrna surveillance and decapping. Structure. 2012 Dec 5;20(12):2025-37. doi: 10.1016/j.str.2012.09.009. Epub 2012, Oct 18. PMID:23085078 doi:https://dx.doi.org/10.1016/j.str.2012.09.009

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4b6h | pdb_00004b6h

Structure of hDcp1a in complex with proline rich sequence of PNRC2

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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