Abstract
The X-ray structure at 2.0-Å resolution of the p90 ribosomal S6 kinase 2 C-terminal kinase domain revealed a C-terminal autoinhibitory αL-helix that was embedded in the kinase scaffold and determines the inactive kinase conformation. We suggest a mechanism of activation through displacement of the αL-helix and rearrangement of the conserved residue Glu500, as well as the reorganization of the T-loop into the active conformation.
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Acknowledgements
Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Basic Energy Sciences, under contract DE-AC02-06CH11357. Part of this work was conducted at the Northeastern Collaborative Access Team, Sector 24-ID, supported by award RR-15301 from the US National Center for Research Resources at the National Institutes of Health. Use of the General Medicine and Cancer Institutes Collaborative Access Team Sector 23-ID was funded with federal funds from the US National Cancer Institute (Y1-CO-1020) and National Institute of General Medical Science (Y1-GM-1104). Other funding was provided by The Hormel Foundation and US National Institutes of Health grants CA111356, CA111536, CA077646, CA081064 and CA120388.
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M.M. conducted cloning, protein purification and crystallization. V.T. performed data collection and X-ray structure determination. V.T. and M.M. performed structural analysis. S.-Y.L. conducted experiments with frog embryos. K.Y. and Y.-Y.C. assisted in the experiments. V.T. and M.M. wrote the manuscript with contributions from A.B. Z.D. supervised and ensured implementation of the project.
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Supplementary Figures 1–4, Supplementary Table 1, Supplementary Methods (PDF 327 kb)
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Malakhova, M., Tereshko, V., Lee, SY. et al. Structural basis for activation of the autoinhibitory C-terminal kinase domain of p90 RSK2. Nat Struct Mol Biol 15, 112–113 (2008). https://doi.org/10.1038/nsmb1347
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DOI: https://doi.org/10.1038/nsmb1347
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