AMP-activated protein kinase (AMPK) is a heterotrimeric complex composed of α catalytic subunit, β scaffolding subunit, and γ regulatory subunit with critical roles in maintaining cellular energy homeostasis. However, the molecular architecture of the intact complex and the allostery associated with the adenosine binding-induced regulation of kinase activity remain unclear. Here, we determine the three-dimensional reconstruction and subunit organization of the full-length rat AMPK (α1β1γ1) through single-particle electron-microscopy. By comparing the structures of AMPK in ATP- and AMP-bound states, we are able to visualize the sequential conformational changes underlying kinase activation that transmits from the adenosine binding sites in the γ subunit to the kinase domain of the α subunit. These results not only make substantial revision to the current model of AMPK assembly, but also highlight a central role of the linker sequence of the α subunit in mediating the allostery of AMPK. © 2011 Elsevier Ltd. All rights reserved.
Zhu, L., Chen, L., Zhou, X. M., Zhang, Y. Y., Zhang, Y. J., Zhao, J., … Wu, Y. (2011). Structural insights into the architecture and allostery of full-length AMP-activated protein kinase. Structure, 19(4), 515–522. https://doi.org/10.1016/j.str.2011.01.018