4B6H: Structure Of Hdcp1a In Complex With Proline Rich Sequence Of Pnrc2

Citation:
Abstract
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.
PDB ID: 4B6HDownload
MMDB ID: 108102
PDB Deposition Date: 2012/8/13
Updated in MMDB: 2013/03
Experimental Method:
x-ray diffraction
Resolution: 2.6  Å
Source Organism:
Similar Structures:
Biological Unit for 4B6H: dimeric; determined by author and by software (PISA)
Molecular Components in 4B6H
Label Count Molecule
Proteins (2 molecules)
1
mRNA-decapping Enzyme 1A(Gene symbol: DCP1A)
Molecule annotation
1
Proline-rich Nuclear Receptor Coactivator 2(Gene symbol: PNRC2)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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