Rudolph Michael J, Amodeo Gabriele A, Iram Surtaj H, Hong Seung-Pyo, Pirino Giorgia, Carlson Marian, Tong Liang
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Structure. 2007 Jan;15(1):65-74. doi: 10.1016/j.str.2006.11.014.
AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis in mammals. AMP is believed to control the activity of AMPK by binding to the gamma subunit of this heterotrimeric enzyme. This subunit contains two Bateman domains, each of which is composed of a tandem pair of cystathionine beta-synthase (CBS) motifs. No structural information is currently available on this subunit, and the molecular basis for its interactions with AMP is not well understood. We report here the crystal structure at 1.9 Angstrom resolution of the Bateman2 domain of Snf4, the gamma subunit of the yeast ortholog of AMPK. The structure revealed a dimer of the Bateman2 domain, and this dimerization is supported by our light-scattering, mutagenesis, and biochemical studies. There is a prominent pocket at the center of this dimer, and most of the disease-causing mutations are located in or near this pocket.
AMP激活的蛋白激酶（AMPK）是哺乳动物能量稳态的核心调节因子。据信，AMP通过与这种异源三聚体酶的γ亚基结合来控制AMPK的活性。该亚基包含两个贝特曼结构域，每个结构域由一对串联的胱硫醚β-合酶（CBS）基序组成。目前尚无关于该亚基的结构信息，其与AMP相互作用的分子基础也尚未完全了解。我们在此报告了AMPK酵母同源物的γ亚基Snf4的贝特曼2结构域在1.9埃分辨率下的晶体结构。该结构揭示了贝特曼2结构域的二聚体，我们的光散射、诱变和生化研究也证实了这种二聚化。在这个二聚体的中心有一个突出的口袋，大多数致病突变都位于这个口袋内或其附近。
