4NH6

Structure of human Dicer Platform-PAZ-Connector Helix cassette in complex with 15-mer siRNA having 5'-pUUU and UU-3' ends (2.55 Angstrom resolution)

Summary for 4NH6

• Entry DOI: 10.2210/pdb4nh6/pdb
• Related: 4NGB 4NGC 4NGD 4NGF 4NGG 4NH3 4NH5 4NHA
• Descriptor: Endoribonuclease Dicer, 5'-R(P*UP*UP*UP*GP*CP*GP*AP*AP*UP*UP*CP*GP*CP*UP*U)-3' (3 entities in total)
• Functional Keywords: paz domain, platform domain, connector helix, sirna, rnase iii domain, endoribonuclease, pre-mirna, hydrolase-rna complex, hydrolase/rna
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : Q9UPY3
• Total number of polymer chains: 2
• Total formula weight: 39636.11

Authors

Simanshu, D.K.,Tian, Y.,Patel, D.J. (deposition date: 2013-11-04, release date: 2014-03-05, Last modification date: 2023-09-20)

Primary citation

Tian, Y.,Simanshu, D.K.,Ma, J.B.,Park, J.E.,Heo, I.,Kim, V.N.,Patel, D.J.
A Phosphate-Binding Pocket within the Platform-PAZ-Connector Helix Cassette of Human Dicer.
Mol.Cell, 53:606-616, 2014

PubMed Abstract: We have solved two families of crystal structures of the human Dicer "platform-PAZ-connector helix" cassette in complex with small interfering RNAs (siRNAs). The structures possess two adjacently positioned pockets: a 2 nt 3'-overhang-binding pocket within the PAZ domain (3' pocket) and a phosphate-binding pocket within the platform domain (phosphate pocket). One family of complexes contains a knob-like α-helical protrusion, designated "hDicer-specific helix," that separates the two pockets and orients the bound siRNA away from the surface of Dicer, which could be indicative of a product release/transfer state. In the second complex, the helical protrusion is melted/disordered and the bound siRNA is aligned toward the surface of Dicer, suggestive of a cleavage-competent state. These structures allow us to propose that the transition from the cleavage-competent to the postulated product release/transfer state may involve release of the 5'-phosphate from the phosphate pocket while retaining the 3' overhang in the 3' pocket.

PubMed: 24486018
DOI: 10.1016/j.molcel.2014.01.003

Experimental method

X-RAY DIFFRACTION (2.551 Å)