2QLV

Crystal structure of the heterotrimer core of the S. cerevisiae AMPK homolog SNF1

Summary for 2QLV

• Entry DOI: 10.2210/pdb2qlv/pdb
• Descriptor: Carbon catabolite derepressing protein kinase, Protein SIP2, Nuclear protein SNF4, ... (4 entities in total)
• Functional Keywords: heterotrimer, atp-binding, carbohydrate metabolism, kinase, membrane, nucleotide-binding, nucleus, phosphorylation, serine/threonine-protein kinase, transferase, lipoprotein, myristate, cbs domain, transcription, transcription regulation, transferase-protein binding complex, transferase/protein binding
• Biological source: Saccharomyces cerevisiae (baker's yeast); More
• Cellular location: Cytoplasm : P06782 P34164; Nucleus : P12904
• Total number of polymer chains: 6
• Total formula weight: 168355.84

Authors

Amodeo, G.A.,Rudolph, M.J.,Tong, L. (deposition date: 2007-07-13, release date: 2007-09-25, Last modification date: 2024-02-21)

Primary citation

Amodeo, G.A.,Rudolph, M.J.,Tong, L.
Crystal structure of the heterotrimer core of Saccharomyces cerevisiae AMPK homologue SNF1.
Nature, 449:492-495, 2007

PubMed Abstract: AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis in mammals and is an attractive target for drug discovery against diabetes, obesity and other diseases. The AMPK homologue in Saccharomyces cerevisiae, known as SNF1, is essential for responses to glucose starvation as well as for other cellular processes, although SNF1 seems to be activated by a ligand other than AMP. Here we report the crystal structure at 2.6 A resolution of the heterotrimer core of SNF1. The ligand-binding site in the gamma-subunit (Snf4) has clear structural differences from that of the Schizosaccharomyces pombe enzyme, although our crystallographic data indicate that AMP can also bind to Snf4. The glycogen-binding domain in the beta-subunit (Sip2) interacts with Snf4 in the heterotrimer but should still be able to bind carbohydrates. Our structure is supported by a large body of biochemical and genetic data on this complex. Most significantly, the structure reveals that part of the regulatory sequence in the alpha-subunit (Snf1) is sequestered by Snf4, demonstrating a direct interaction between the alpha- and gamma-subunits and indicating that our structure may represent the heterotrimer core of SNF1 in its activated state.

PubMed: 17851534
DOI: 10.1038/nature06127

Experimental method

X-RAY DIFFRACTION (2.6 Å)