TY - JOUR
T1 - Crystal Structure of Silkworm PIWI-Clade Argonaute Siwi Bound to piRNA
AU - Matsumoto, Naoki
AU - Nishimasu, Hiroshi
AU - Sakakibara, Kazuhiro
AU - Nishida, Kazumichi M.
AU - Hirano, Takamasa
AU - Ishitani, Ryuichiro
AU - Siomi, Haruhiko
AU - Siomi, Mikiko C.
AU - Nureki, Osamu
N1 - Funding Information:
We thank Akira Oe for assistance with sample preparation, Takashi Yamano for assistance with data collection, Dr. Takanori Nakane and Dr. Tomohiro Nishizawa for assistance with model building, and the beamline scientists at SPring-8 BL41XU for assistance with data collection. This research was supported by the Platform Project for Supporting in Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from the Japan Agency for Medical Research and Development (AMED). H.N., K.M.N., H.S., and M.C.S. were supported by a Grant-in-Aid for Scientific Research, from the Ministry of Education, Culture, Sports, Science and Technology of Japan ( 26291010 and 15H01463 to H.N., 15K06948 to K.M.N., 25221003 to H.S., and 25221101 to M.C.S.). O.N. was supported by the Core Research for Evolutional Science and Technology (CREST) Program, The Creation of Basic Medical Technologies to Clarify and Control the Mechanisms Underlying Chronic Inflammation of Japan Science and Technology Agency (JST).
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/10/6
Y1 - 2016/10/6
N2 - PIWI-clade Argonaute proteins associate with PIWI-interacting RNAs (piRNAs) and silence transposable elements in animal gonads. Here, we report the crystal structure of a silkworm PIWI-clade Argonaute, Siwi, bound to the endogenous piRNA, at 2.4 Å resolution. Siwi adopts a bilobed architecture consisting of N-PAZ and MID-PIWI lobes, in which the 5′ and 3′ ends of the bound piRNA are anchored by the MID-PIWI and PAZ domains, respectively. A structural comparison of Siwi with AGO-clade Argonautes reveals notable differences in their nucleic-acid-binding channels, likely reflecting the distinct lengths of their guide RNAs and their mechanistic differences in guide RNA loading and cleavage product release. In addition, the structure reveals that Siwi and prokaryotic, but not eukaryotic, AGO-clade Argonautes share unexpected similarities, such as metal-dependent 5′-phosphate recognition and a potential structural transition during the catalytic-tetrad formation. Overall, this study provides a critical starting point toward a mechanistic understanding of piRNA-mediated transposon silencing.
AB - PIWI-clade Argonaute proteins associate with PIWI-interacting RNAs (piRNAs) and silence transposable elements in animal gonads. Here, we report the crystal structure of a silkworm PIWI-clade Argonaute, Siwi, bound to the endogenous piRNA, at 2.4 Å resolution. Siwi adopts a bilobed architecture consisting of N-PAZ and MID-PIWI lobes, in which the 5′ and 3′ ends of the bound piRNA are anchored by the MID-PIWI and PAZ domains, respectively. A structural comparison of Siwi with AGO-clade Argonautes reveals notable differences in their nucleic-acid-binding channels, likely reflecting the distinct lengths of their guide RNAs and their mechanistic differences in guide RNA loading and cleavage product release. In addition, the structure reveals that Siwi and prokaryotic, but not eukaryotic, AGO-clade Argonautes share unexpected similarities, such as metal-dependent 5′-phosphate recognition and a potential structural transition during the catalytic-tetrad formation. Overall, this study provides a critical starting point toward a mechanistic understanding of piRNA-mediated transposon silencing.
KW - 1U bias
KW - Argonaute
KW - PIWI
KW - RNA silencing
KW - Siwi
KW - piRNA
KW - small RNA
KW - x-ray crystallography
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U2 - 10.1016/j.cell.2016.09.002
DO - 10.1016/j.cell.2016.09.002
M3 - Article
C2 - 27693359
AN - SCOPUS:84990913683
SN - 0092-8674
VL - 167
SP - 484-497.e9
JO - Cell
JF - Cell
IS - 2
ER -