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Science, Published online 29 July 2004
Crystal Structure of Argonaute and Its Implications for RISC Slicer Activity
Abstract
Ji-Joon Song 1, Stephanie K. Smith 2, Gregory J. Hannon 3, Leemor Joshua-Tor 1*
1 Watson School of Biological Sciences, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA; Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
2 Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
3 Watson School of Biological Sciences, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
* To whom correspondence should be addressed. Leemor Joshua-Tor
Argonaute proteins and siRNAs are the known signature components of the RNAi effector complex, RISC. However, the identity of "Slicer," the enzyme that cleaves the mRNA as directed by the siRNA has not been resolved. Here, we report the crystal structure of the Argonaute protein from Pyrococcus furiosus at 2.25Å resolution. The structure reveals a crescent-shaped base made up of the N-terminal, middle and PIWI domains. The PAZ domain is held above the base by a "stalk"-like region. The PIWI domain is similar to RNase H, with a conserved active site DDE motif, strongly implicating Argonaute as "Slicer." The architecture of the molecule and placement of the PAZ and PIWI domains define a groove for substrate binding and suggest a mechanism for siRNA guided mRNA cleavage.
1 Watson School of Biological Sciences, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA; Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
2 Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
3 Watson School of Biological Sciences, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
* To whom correspondence should be addressed. Leemor Joshua-Tor
Argonaute proteins and siRNAs are the known signature components of the RNAi effector complex, RISC. However, the identity of "Slicer," the enzyme that cleaves the mRNA as directed by the siRNA has not been resolved. Here, we report the crystal structure of the Argonaute protein from Pyrococcus furiosus at 2.25Å resolution. The structure reveals a crescent-shaped base made up of the N-terminal, middle and PIWI domains. The PAZ domain is held above the base by a "stalk"-like region. The PIWI domain is similar to RNase H, with a conserved active site DDE motif, strongly implicating Argonaute as "Slicer." The architecture of the molecule and placement of the PAZ and PIWI domains define a groove for substrate binding and suggest a mechanism for siRNA guided mRNA cleavage.
논문정보
- Research article
- 2004년 08월 (BRIC 등록일 )
- 국외 연구진
- 생명과학 > 구조생물 및 생물물리학
- 120회 이상 인용된 논문 (상위피인용논문 등록일 2009-08-23)
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