3QB5

Human C3PO complex in the presence of MnSO4

Summary for 3QB5

• Entry DOI: 10.2210/pdb3qb5/pdb
• Related: 3PJA
• Descriptor: Translin, Translin-associated protein X, SODIUM ION, ... (8 entities in total)
• Functional Keywords: 7 alpha helical bundle, ribonuclease, hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q15631; Cytoplasm, perinuclear region: Q99598
• Total number of polymer chains: 4
• Total formula weight: 112314.83

Authors

Ye, X.,Huang, N.,Liu, Y.,Paroo, Z.,Chen, S.,Zhang, H.,Liu, Q. (deposition date: 2011-01-12, release date: 2011-05-11, Last modification date: 2023-09-13)

Primary citation

Ye, X.,Huang, N.,Liu, Y.,Paroo, Z.,Huerta, C.,Li, P.,Chen, S.,Liu, Q.,Zhang, H.
Structure of C3PO and mechanism of human RISC activation.
Nat.Struct.Mol.Biol., 18:650-657, 2011

PubMed Abstract: Assembly 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.

PubMed: 21552258
DOI: 10.1038/nsmb.2032

Experimental method

X-RAY DIFFRACTION (2.95 Å)