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A Phosphate-Binding Pocket within the Platform-PAZ-Connector Helix Cassette of Human Dicer

Cited 75 time in Web of Science Cited 79 time in Scopus
Issue Date
2014-02
Citation
Molecular Cell, Vol.53 No.4, pp.606-616
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 alpha-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.
ISSN
1097-2765
URI
https://hdl.handle.net/10371/171866
DOI
https://doi.org/10.1016/j.molcel.2014.01.003
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College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
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