3qb5
From Proteopedia
Human C3PO complex in the presence of MnSO4
Structural highlights
Function[TSN_HUMAN] DNA-binding protein that specifically recognizes consensus sequences at the breakpoint junctions in chromosomal translocations, mostly involving immunoglobulin (Ig)/T-cell receptor gene segments. Seems to recognize single-stranded DNA ends generated by staggered breaks occurring at recombination hot spots.[1] [2] Exhibits both single-stranded and double-stranded endoribonuclease activity. May act as an activator of RNA-induced silencing complex (RISC) by facilitating endonucleolytic cleavage of the siRNA passenger strand.[3] [4] [TSNAX_HUMAN] Acts in combination with TSN as an endonuclease involved in the activation of the RNA-induced silencing complex (RISC). Possible role in spermatogenesis.[5] [6] Publication Abstract from PubMedAssembly of the RNA-induced silencing complex (RISC) consists of loading duplex (guide-passenger) siRNA onto Argonaute (Ago2) and removing the passenger strand. Ago2 contributes critically to RISC activation by nicking the passenger strand. Here we reconstituted duplex siRNA-initiated RISC activity using recombinant human Ago2 (hAgo2) and C3PO, indicating that C3PO has a critical role in hAgo2-RISC activation. Consistently, genetic depletion of C3PO compromised RNA silencing in mammalian cells. We determined the crystal structure of hC3PO, which reveals an asymmetric octamer barrel consisting of six translin and two TRAX subunits. This asymmetric assembly is critical for the function of C3PO as an endonuclease that cleaves RNA at the interior surface. The current work supports a Dicer-independent mechanism for human RISC activation, in which Ago2 directly binds duplex siRNA and nicks the passenger strand, and then C3PO activates RISC by degrading the Ago2-nicked passenger strand. Structure of C3PO and mechanism of human RISC activation.,Ye X, Huang N, Liu Y, Paroo Z, Huerta C, Li P, Chen S, Liu Q, Zhang H Nat Struct Mol Biol. 2011 May 8. PMID:21552258[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Large Structures | Chen, S | Huang, N | Liu, Q | Liu, Y | Paroo, Z | Ye, X | Zhang, H | Alpha helical bundle | Hydrolase | Ribonuclease