3d45

From Proteopedia

Crystal structure of mouse PARN in complex with m7GpppG

PDB ID 3d45

Drag the structure with the mouse to rotate

Structural highlights

3d45 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PARN_MOUSE 3'-exoribonuclease that has a preference for poly(A) tails of mRNAs, thereby efficiently degrading poly(A) tails. Exonucleolytic degradation of the poly(A) tail is often the first step in the decay of eukaryotic mRNAs and is also used to silence certain maternal mRNAs translationally during oocyte maturation and early embryonic development. Interacts with both the 3'-end poly(A) tail and the 5'-end cap structure during degradation, the interaction with the cap structure being required for an efficient degradation of poly(A) tails. Involved in nonsense-mediated mRNA decay, a critical process of selective degradation of mRNAs that contain premature stop codons. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly via its interaction with KHSRP. Probably mediates the removal of poly(A) tails of AREs mRNAs, which constitutes the first step of destabilization (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Poly(A)-specific ribonuclease (PARN) is a homodimeric, processive, and cap-interacting 3' exoribonuclease that efficiently degrades eukaryotic mRNA poly(A) tails. The crystal structure of a C-terminally truncated PARN in complex with m(7)GpppG reveals that, in one subunit, m(7)GpppG binds to a cavity formed by the RRM domain and the nuclease domain, whereas in the other subunit, it binds almost exclusively to the RRM domain. Importantly, our structural and competition data show that the cap-binding site overlaps with the active site in the nuclease domain. Mutational analysis demonstrates that residues involved in m(7)G recognition are crucial for cap-stimulated deadenylation activity, and those involved in both cap and poly(A) binding are important for catalysis. A modeled PARN, which shows that the RRM domain from one subunit and the R3H domain from the other subunit enclose the active site, provides a structural foundation for further studies to elucidate the mechanism of PARN-mediated deadenylation.

Structural basis of m(7)GpppG binding to poly(A)-specific ribonuclease.,Wu M, Nilsson P, Henriksson N, Niedzwiecka A, Lim MK, Cheng Z, Kokkoris K, Virtanen A, Song H Structure. 2009 Feb 13;17(2):276-86. doi: 10.1016/j.str.2008.11.012. PMID:19217398^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wu M, Nilsson P, Henriksson N, Niedzwiecka A, Lim MK, Cheng Z, Kokkoris K, Virtanen A, Song H. Structural basis of m(7)GpppG binding to poly(A)-specific ribonuclease. Structure. 2009 Feb 13;17(2):276-86. doi: 10.1016/j.str.2008.11.012. PMID:19217398 doi:http://dx.doi.org/10.1016/j.str.2008.11.012