2Y35

Crystal structure of Xrn1-substrate complex

Summary for 2Y35

• Entry DOI: 10.2210/pdb2y35/pdb
• Descriptor: LD22664P, DT11 (5'-D(*TP*TP*TP*TP*TP*TP*TP*TP*TP*TP*TP)-3', MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: hydrolase-dna complex, rna degradation, exonuclease 5'-3', rna interference, hydrolase/dna
• Biological source: DROSOPHILA MELANOGASTER (FRUIT FLY); More
• Total number of polymer chains: 2
• Total formula weight: 135721.44

Authors

Jinek, M.,Coyle, S.M.,Doudna, J.A. (deposition date: 2010-12-18, release date: 2011-03-16, Last modification date: 2024-05-08)

Primary citation

Jinek, M.,Coyle, S.M.,Doudna, J.A.
Coupled 5' Nucleotide Recognition and Processivity in Xrn1-Mediated Mrna Decay.
Mol.Cell, 41:600-, 2011

PubMed Abstract: Messenger RNA decay plays a central role in the regulation and surveillance of eukaryotic gene expression. The conserved multidomain exoribonuclease Xrn1 targets cytoplasmic RNA substrates marked by a 5' monophosphate for processive 5'-to-3' degradation by an unknown mechanism. Here, we report the crystal structure of an Xrn1-substrate complex. The single-stranded substrate is held in place by stacking of the 5'-terminal trinucleotide between aromatic side chains while a highly basic pocket specifically recognizes the 5' phosphate. Mutations of residues involved in binding the 5'-terminal nucleotide impair Xrn1 processivity. The substrate recognition mechanism allows Xrn1 to couple processive hydrolysis to duplex melting in RNA substrates with sufficiently long single-stranded 5' overhangs. The Xrn1-substrate complex structure thus rationalizes the exclusive specificity of Xrn1 for 5'-monophosphorylated substrates, ensuring fidelity of mRNA turnover, and posits a model for translocation-coupled unwinding of structured RNA substrates.

PubMed: 21362555
DOI: 10.1016/J.MOLCEL.2011.02.004

Experimental method

X-RAY DIFFRACTION (3.2 Å)