TY - JOUR
T1 - Structural Insight into AMPK Regulation
T2 - ADP Comes into Play
AU - Jin, Xiangshu
AU - Townley, Robert
AU - Shapiro, Lawrence
N1 - Funding Information:
We acknowledge funding from the NIH (R24 DK071030) and the Naomi Berrie Diabetes Center, and a Jules and Doris Stein Research to Prevent Blindness Foundation professorship award to L.S. X-ray data were acquired at the Northeastern Collaborative Access Team beamlines of the Advanced Photon Source, supported by award RR-15301 from the National Center for Research Resources at the National Institutes of Health. Use of the Advanced Photon Source is supported by the U.S. Department of Energy, Office of Basic Energy Sciences, under contract DE-AC02-06CH11357.
PY - 2007/10/16
Y1 - 2007/10/16
N2 - The AMP-activated protein kinase (AMPK), a sensor of cellular energy status found in all eukaryotes, responds to changes in intracellular adenosine nucleotide levels resulting from metabolic stresses. Here we describe crystal structures of a heterotrimeric regulatory core fragment from Schizosaccharomyces pombe AMPK in complex with ADP, ADP/AMP, ADP/ATP, and 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranotide (AICAR phosphate, or ZMP), a well-characterized AMPK activator. Prior crystallographic studies had revealed a single site in the γ subunit that binds either ATP or AMP within Bateman domain B. Here we show that ZMP binds at this site, mimicking the binding of AMP. An analogous site in Bateman domain A selectively accommodates ADP, which binds in a distinct manner that also involves direct ligation to elements from the β subunit. These observations suggest a possible role for ADP in regulating AMPK response to changes in cellular energy status.
AB - The AMP-activated protein kinase (AMPK), a sensor of cellular energy status found in all eukaryotes, responds to changes in intracellular adenosine nucleotide levels resulting from metabolic stresses. Here we describe crystal structures of a heterotrimeric regulatory core fragment from Schizosaccharomyces pombe AMPK in complex with ADP, ADP/AMP, ADP/ATP, and 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranotide (AICAR phosphate, or ZMP), a well-characterized AMPK activator. Prior crystallographic studies had revealed a single site in the γ subunit that binds either ATP or AMP within Bateman domain B. Here we show that ZMP binds at this site, mimicking the binding of AMP. An analogous site in Bateman domain A selectively accommodates ADP, which binds in a distinct manner that also involves direct ligation to elements from the β subunit. These observations suggest a possible role for ADP in regulating AMPK response to changes in cellular energy status.
KW - SIGNALING
UR - http://www.scopus.com/inward/record.url?scp=35148850705&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35148850705&partnerID=8YFLogxK
U2 - 10.1016/j.str.2007.07.017
DO - 10.1016/j.str.2007.07.017
M3 - Article
C2 - 17937917
AN - SCOPUS:35148850705
SN - 0969-2126
VL - 15
SP - 1285
EP - 1295
JO - Structure
JF - Structure
IS - 10
ER -