3d45
From Proteopedia
Crystal structure of mouse PARN in complex with m7GpppG
Structural highlights
FunctionPARN_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 PubMedPoly(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. See AlsoReferences
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