title: Structural insights into the architecture and allostery of full-length AMP-activated protein kinase.
abstract: 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.
authors.affiliation: MOE Key Laboratory of Arid and Grassland Ecology, Institute of Biophysics, Lanzhou University, Lanzhou 730000, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Zhou
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhang
authors.forename: Yi-Jiong
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Shang-Rong
authors.initials: SR
authors.lastname: Ji
authors.forename: Jia-Wei
authors.initials: JW
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000495:Allosteric Site; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D055162:Biocatalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D008854:Microscopy, Electron; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051381:Rats
chemical_list: D021122:Protein Subunits; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D055372:AMP-Activated Protein Kinases