4WYQ

Crystal structure of the Dicer-TRBP interface

Summary for 4WYQ

• Entry DOI: 10.2210/pdb4wyq/pdb
• Descriptor: Endoribonuclease Dicer, RISC-loading complex subunit TARBP2, Poly(UNK) (3 entities in total)
• Functional Keywords: rna interference, microrna, dsrbp, dsrbd, hydrolase-protein binding complex, hydrolase/protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 47024.95

Authors

Wilson, R.C.,Doudna, J.A. (deposition date: 2014-11-18, release date: 2014-12-17, Last modification date: 2024-10-16)

Primary citation

Wilson, R.C.,Tambe, A.,Kidwell, M.A.,Noland, C.L.,Schneider, C.P.,Doudna, J.A.
Dicer-TRBP Complex Formation Ensures Accurate Mammalian MicroRNA Biogenesis.
Mol.Cell, 57:397-407, 2015

PubMed Abstract: RNA-mediated gene silencing in human cells requires the accurate generation of ∼22 nt microRNAs (miRNAs) from double-stranded RNA substrates by the endonuclease Dicer. Although the phylogenetically conserved RNA-binding proteins TRBP and PACT are known to contribute to this process, their mode of Dicer binding and their genome-wide effects on miRNA processing have not been determined. We solved the crystal structure of the human Dicer-TRBP interface, revealing the structural basis of the interaction. Interface residues conserved between TRBP and PACT show that the proteins bind to Dicer in a similar manner and by mutual exclusion. Based on the structure, a catalytically active Dicer that cannot bind TRBP or PACT was designed and introduced into Dicer-deficient mammalian cells, revealing selective defects in guide strand selection. These results demonstrate the role of Dicer-associated RNA binding proteins in maintenance of gene silencing fidelity.

PubMed: 25557550
DOI: 10.1016/j.molcel.2014.11.030

Experimental method

X-RAY DIFFRACTION (3.2 Å)