Structural highlights
Function
[PAN3_NEUCR] Regulatory subunit of the poly(A)-nuclease (PAN) deadenylation complex involved in cytoplasmic mRNA turnover. PAN specifically shortens poly(A) tails of RNA when the poly(A) stretch is bound by polyadenylate-binding protein pab-1. Deadenylation of the 3'-tail to a length that is too short to bind pab-1 induces mRNA decay. May also be involved in post-transcriptional maturation of mRNA poly(A) tails. pan-3 acts as a positive regulator for PAN activity, recruiting pan-2 to mRNA via its interaction with pab-1 (By similarity).
Publication Abstract from PubMed
The PAN2-PAN3 deadenylase complex functions in general and miRNA-mediated mRNA degradation and is specifically recruited to miRNA targets by GW182/TNRC6 proteins. We describe the PAN3 adaptor protein crystal structure that, unexpectedly, forms intertwined and asymmetric homodimers. Dimerization is mediated by a coiled coil that links an N-terminal pseudokinase to a C-terminal knob domain. The PAN3 pseudokinase binds ATP, and this function is required for mRNA degradation in vivo. We further identified conserved surfaces required for mRNA degradation, including the binding surface for the PAN2 deadenylase on the knob domain. The most remarkable structural feature is the presence of a tryptophan-binding pocket at the dimer interface, which mediates binding to TNRC6C in human cells. Together, our data reveal the structural basis for the interaction of PAN3 with PAN2 and the recruitment of the PAN2-PAN3 complex to miRNA targets by TNRC6 proteins.
Structure of the PAN3 Pseudokinase Reveals the Basis for Interactions with the PAN2 Deadenylase and the GW182 Proteins.,Christie M, Boland A, Huntzinger E, Weichenrieder O, Izaurralde E Mol Cell. 2013 Aug 8;51(3):360-73. doi: 10.1016/j.molcel.2013.07.011. PMID:23932717[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Christie M, Boland A, Huntzinger E, Weichenrieder O, Izaurralde E. Structure of the PAN3 Pseudokinase Reveals the Basis for Interactions with the PAN2 Deadenylase and the GW182 Proteins. Mol Cell. 2013 Aug 8;51(3):360-73. doi: 10.1016/j.molcel.2013.07.011. PMID:23932717 doi:10.1016/j.molcel.2013.07.011
