The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Small Molecules CK-666 and CK-869 Inhibit Actin-Related Protein 2/3 Complex by Blocking an Activating Conformational Change
Open accessAbstract
Summary Arp2/3 complex is a seven-subunit assembly that nucleates branched actin filaments. Small molecule inhibitors CK-666 and CK-869 bind to Arp2/3 complex and inhibit nucleation, but their modes of action are unknown. Here we use biochemical and structural methods to determine the mechanism of each inhibitor. Our data indicate that CK-666 stabilizes the inactive state of the complex, blocking movement of the Arp2 and Arp3 subunits into the activated filament-like (short pitch) conformation, while CK-869 binds to a serendipitous pocket on Arp3 and allosterically destabilizes the short pitch Arp3-Arp2 interface. These results provide key insights into the relationship between conformation and activity in Arp2/3 complex, and will be critical for interpreting the influence of the inhibitors on actin filament networks in vivo.
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Self-citation
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Jayatilaka, H., Tyle, P., Chen, J. J., Kwak, M., Ju, J., Kim, H. J., Lee, J. S. H., Wu, P.-H., Gilkes, D. M., Fan, R., et al. (2017) · Nature Communications · doi:10.1038/ncomms15584 · Cited by 177
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Metadata
- Authors
- Hetrick, B., Han, M. S., Helgeson, L. A., & Nolen, B. J.
- Venue
- Chemistry & Biology
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 20
- Issue
- 5
- Pages
- 701-712
- ISSN
- 1074-5521 (ISSN-L)
- OpenAlex
- W2075871987
- Cited by
- 353
- References
- 51
- FWCI
- 8.41
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hetrick, B., Han, M. S., Helgeson, L. A., & Nolen, B. J. (2013). Small Molecules CK-666 and CK-869 Inhibit Actin-Related Protein 2/3 Complex by Blocking an Activating Conformational Change. Chemistry & Biology. https://doi.org/10.1016/j.chembiol.2013.03.019
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