Abstract
The energy sensor AMP-activated protein kinase (AMPK) is a heterotrimeric complex that is allosterically activated by AMP binding to the γ subunit. Cocrystal structures of the mammalian AMPK core reveal occlusion of nucleotide-binding site 3 of the γ subunit in the presence of ATP. However, site 3 is occupied in the presence of AMP. Mutagenesis studies indicate that sites 3 and 4 are important for AMPK allosteric activation.
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Acknowledgements
We thank S.C. Lin for critical discussions and reading of the manuscript. Crystallographic data were collected at Shanghai Synchrotron Radiation Facility beamline 17U. This work is supported in part by grant 2011CB910800 (National Key Basic Research Program of China) to J.-W.W. and Z.-X.W. and grants 31130062, 31070643 (Natural Science Foundation of China) and 09THZ02235 (Tsinghua University) to J.-W.W.
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L.C., J.W. and Y.-Y.Z. performed experiments; S.F.Y., D.N., U.S., Z.-X.W. and J.-W.W. contributed to discussions and manuscript writing.
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Chen, L., Wang, J., Zhang, YY. et al. AMP-activated protein kinase undergoes nucleotide-dependent conformational changes. Nat Struct Mol Biol 19, 716–718 (2012). https://doi.org/10.1038/nsmb.2319
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DOI: https://doi.org/10.1038/nsmb.2319
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