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The Structure of Human Argonaute-2 in Complex with miR-20a
Open accessAbstract
SUMMARY Argonaute proteins lie at the heart of the RNA-induced silencing complex (RISC), wherein they use small RNA guides to recognize targets. Initial insight into the architecture of Argonautes came from studies of prokaryotic proteins, revealing a crescent-shaped base made up of the amino-terminal, PAZ, middle, and PIWI domains. The recently reported crystal structure of human Argonaute-2 (hAgo2), the “slicer” in RNA interference, in complex with a mixed population of RNAs derived from insect cells provides insight into the architecture of a eukaryotic Argonaute protein with defined biochemical and biological functions. Here, we report the structure of human Ago2 bound to a physiologically relevant microRNA, microRNA-20a, at 2.2 Å resolution. The miRNA is anchored at both ends by the Mid and PAZ domains and makes several kinks and turns along the binding groove. Interestingly, miRNA binding confers remarkable stability on hAgo2, locking this otherwise flexible enzyme into a stable conformation.
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PHENIX : a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L.-W., Kapral, G. J., Grosse-Kunstleve, R. W., et al. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909052925 · Cited by 23,716
MicroRNAs: Target Recognition and Regulatory Functions
Bartel, D. P. (2009) · Cell · doi:10.1016/j.cell.2009.01.002 · Cited by 20,068
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Ameres, S. L., & Zamore, P. D. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3611 · Cited by 1,175
Metadata
- Authors
- Elkayam, E., Kuhn, C.-D., Tocilj, A., Haase, A. D., Greene, E. M., Hannon, G. J., & Joshua-Tor, L.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 150
- Issue
- 1
- Pages
- 100-110
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2139115320
- Cited by
- 613
- References
- 2
- FWCI
- 20.21
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Elkayam, E., Kuhn, C.-D., Tocilj, A., Haase, A. D., Greene, E. M., Hannon, G. J., & Joshua-Tor, L. (2012). The Structure of Human Argonaute-2 in Complex with miR-20a. Cell. https://doi.org/10.1016/j.cell.2012.05.017
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