2YHB

Crystal Structure of the N. crassa QDE-2 AGO MID-PIWI Domains

Summary for 2YHB

• Entry DOI: 10.2210/pdb2yhb/pdb
• Related: 2XDY 2YHA
• Descriptor: POST-TRANSCRIPTIONAL GENE SILENCING PROTEIN QDE-2, SULFATE ION, GLYCEROL (3 entities in total)
• Functional Keywords: rna binding protein, argonaute, mirna, sirna
• Biological source: NEUROSPORA CRASSA
• Total number of polymer chains: 1
• Total formula weight: 49065.28

Authors

Boland, A.,Weichenrieder, O. (deposition date: 2011-04-27, release date: 2011-06-15, Last modification date: 2023-12-20)

Primary citation

Boland, A.,Huntzinger, E.,Schmidt, S.,Izaurralde, E.,Weichenriede, O.
Crystal Structure of the Mid-Piwi Lobe of a Eukaryotic Argonaute Protein
Proc.Natl.Acad.Sci.USA, 108:10466-, 2011

PubMed Abstract: Argonaute proteins (AGOs) are essential effectors in RNA-mediated gene silencing pathways. They are characterized by a bilobal architecture, in which one lobe contains the N-terminal and PAZ domains and the other contains the MID and PIWI domains. Here, we present the first crystal structure of the MID-PIWI lobe from a eukaryotic AGO, the Neurospora crassa QDE-2 protein. Compared to prokaryotic AGOs, the domain orientation is conserved, indicating a conserved mode of nucleic acid binding. The PIWI domain shows an adaptable surface loop next to a eukaryote-specific α-helical insertion, which are both likely to contact the PAZ domain in a conformation-dependent manner to sense the functional state of the protein. The MID-PIWI interface is hydrophilic and buries residues that were previously thought to participate directly in the allosteric regulation of guide RNA binding. The interface includes the binding pocket for the guide RNA 5' end, and residues from both domains contribute to binding. Accordingly, micro-RNA (miRNA) binding is particularly sensitive to alteration in the MID-PIWI interface in Drosophila melanogaster AGO1 in vivo. The structure of the QDE-2 MID-PIWI lobe provides molecular and mechanistic insight into eukaryotic AGOs and has significant implications for understanding the role of these proteins in silencing.

PubMed: 21646546
DOI: 10.1073/PNAS.1103946108

Experimental method

X-RAY DIFFRACTION (3.65 Å)