Abstract
arising from B. Xiao et al. Nature 472, 230–233 (2011)10.1038/nature09932
The AMP-activated protein kinase (AMPK), an αβγ heterotrimeric enzyme, has a central role in regulating cellular metabolism and energy homeostasis1. The α-subunit of AMPK possesses the catalytic kinase domain, followed by a regulatory region comprising the autoinhibitory domain (AID) and α-linker2,3. Structural and biochemical studies suggested that AID is central to mammalian AMPK regulation4; however, this notion has been challenged recently by Xiao et al. on the basis of their active AMPK structure (Protein Data Bank accession 2Y94)5. On close inspection, however, we found that the α-subunit regulatory region was incorrectly built in their model, and our rebuilt model suggests a universal occurrence of the AID domain in AMPKs; we have also identified a novel regulatory motif that is essential for AMPK regulation.
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L.C., F.-J.X., J.W., Y.-Y.Z., L.-S.C. and C.L. performed the X-ray structural and mutational studies; J.H. and S.W. carried out NMR studies; Z.-X.W., U.S., D.N., B.X., S.F.Y. and P.L. contributed to discussions and manuscript writing; J.-W.W. led the team and wrote the paper. Coordinates have been deposited into the Protein Data Bank with accession codes 4F2L for the rat α1-AID crystal structure and 2LTU for the human α2-AID NMR solution structure, respectively.
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Chen, L., Xin, FJ., Wang, J. et al. Conserved regulatory elements in AMPK. Nature 498, E8–E10 (2013). https://doi.org/10.1038/nature12189
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DOI: https://doi.org/10.1038/nature12189
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