Structural Insight into AMPK Regulation

ADP Comes into Play

Xiangshu Jin, Robert Townley, Lawrence Shapiro

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1285-1295
Number of pages11
JournalStructure
Volume15
Issue number10
DOIs
StatePublished - Oct 16 2007
Externally publishedYes

Fingerprint

AMP-Activated Protein Kinases
Adenosine Diphosphate
Adenosine Monophosphate
Adenosine Triphosphate
Aminoimidazole Carboxamide
Physiological Stress
Schizosaccharomyces
Eukaryota
Adenosine
Ligation
Nucleotides
Phosphates
Binding Sites
AICA ribonucleotide

Keywords

  • SIGNALING

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Structural Insight into AMPK Regulation : ADP Comes into Play. / Jin, Xiangshu; Townley, Robert; Shapiro, Lawrence.

In: Structure, Vol. 15, No. 10, 16.10.2007, p. 1285-1295.

Research output: Contribution to journalArticle

Jin, X, Townley, R & Shapiro, L 2007, 'Structural Insight into AMPK Regulation: ADP Comes into Play', Structure, vol. 15, no. 10, pp. 1285-1295. https://doi.org/10.1016/j.str.2007.07.017
Jin, Xiangshu ; Townley, Robert ; Shapiro, Lawrence. / Structural Insight into AMPK Regulation : ADP Comes into Play. In: Structure. 2007 ; Vol. 15, No. 10. pp. 1285-1295.
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