5ygf
Crystal structure of Drosophila melanogaster Papi extended Tudor domain (D287A) in complex with Piwi N-terminal R10-unme peptide
Structural highlights
FunctionTDRKH_DROME Involved in the piwi-interacting RNA (piRNA) metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins, and governs the methylation and subsequent repression of transposons which is essential for germline integrity (PubMed:21447556, PubMed:29531043). Likely to act by recruiting Piwi proteins such as AGO3 and piwi to the piRNA biogenesis machinery in the nuage (PubMed:21447556, PubMed:29531043). Required for the final steps of primary piRNA biogenesis by participating in the 3' end-trimming of piwi-bound intermediates into mature piRNAs (PubMed:29531043).[1] [2] Publication Abstract from PubMedThe Tudor domain-containing (Tdrd) family proteins play a critical role in transposon silencing in animal gonads by recognizing the symmetrically dimethylated arginine (sDMA) on the (G/A)R motif of the N-terminal of PIWI family proteins via the eTud domains. Papi, also known as "Tdrd2," is involved in Zucchini-mediated PIWI-interacting RNA (piRNA) 3'-end maturation. Intriguingly, a recent study showed that, in papi mutant flies, only Piwi-bound piRNAs increased in length, and not Ago3-bound or Aub-bound piRNAs. However, the molecular and structural basis of the Papi-Piwi complex is still not fully understood, which limits mechanistic understanding of the function of Papi in piRNA biogenesis. In the present study, we determined the crystal structures of Papi-eTud in the apo form and in complex with a peptide containing unmethylated or dimethylated R10 residues. Structural and biochemical analysis showed that the Papi interaction region on the Drosophila Piwi contains an RGRRR motif (R7-R11) distinct from the consensus (G/A)R motif recognized by canonical eTud. Mass spectrometry results indicated that Piwi is the major binding partner of Papi in vivo. The papi mutant flies suffered from both fertility and transposon-silencing defects, supporting the important role conferred to Papi in piRNA 3' processing through direct interaction with Piwi proteins. Structural insights into the sequence-specific recognition of Piwi by Drosophila Papi.,Zhang Y, Liu W, Li R, Gu J, Wu P, Peng C, Ma J, Wu L, Yu Y, Huang Y Proc Natl Acad Sci U S A. 2018 Mar 27;115(13):3374-3379. doi:, 10.1073/pnas.1717116115. Epub 2018 Mar 12. PMID:29531043[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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