[摘要]：AMP-activated protein kinase (AMPK) is a heterotrimeric complex composed of alpha catalytic subunit, beta scaffolding subunit, and gamma 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 (alpha 1 beta 1 gamma 1) 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 gamma subunit to the kinase domain of the alpha 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 a subunit in mediating the allostery of AMPK.
