کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2030406 1071101 2006 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Structure and Dimerization of the Kinase Domain from Yeast Snf1, a Member of the Snf1/AMPK Protein Family
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Structure and Dimerization of the Kinase Domain from Yeast Snf1, a Member of the Snf1/AMPK Protein Family
چکیده انگلیسی

SummaryThe Snf1/AMPK kinases are intracellular energy sensors, and the AMPK pathway has been implicated in a variety of metabolic human disorders. Here we report the crystal structure of the kinase domain from yeast Snf1, revealing a bilobe kinase fold with greatest homology to cyclin-dependant kinase-2. Unexpectedly, the crystal structure also reveals a novel homodimer that we show also forms in solution, as demonstrated by equilibrium sedimentation, and in yeast cells, as shown by coimmunoprecipitation of differentially tagged intact Snf1. A mapping of sequence conservation suggests that dimer formation is a conserved feature of the Snf1/AMPK kinases. The conformation of the conserved αC helix, and the burial of the activation segment and substrate binding site within the dimer, suggests that it represents an inactive form of the kinase. Taken together, these studies suggest another layer of kinase regulation within the Snf1/AMPK family, and an avenue for development of AMPK-specific activating compounds.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 14, Issue 3, March 2006, Pages 477–485
نویسندگان
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