Structural insight into AMPK regulation: ADP comes into play

被引：67

作者：

Jin, Xiangshu

Townley, Robert

Shapiro, Lawrence ^{[1
]}

机构：

[1] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA

[2] Columbia Univ, Naomi Berrie Diabetes Ctr, New York, NY 10032 USA

[3] Columbia Univ, Edward S Harkness Eye Inst, New York, NY 10032 USA

来源：

STRUCTURE | 2007年 / 15卷 / 10期

关键词：

D O I：

10.1016/j.str.2007.07.017

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-beta-Dribofuranotide (AICAR phosphate, or ZMP), a well-characterized AMPK activator. Prior crystallographic studies had revealed a single site in the gamma 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 0 subunit. These observations suggest a possible role for ADP in regulating AMPK response to changes in cellular energy status.

引用

页码：1285 / 1295

页数：11

共 34 条

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