2010/05/06

The Crystal Structure of Protein MJ1225 from Methanocaldococcus jannaschii Shows Strong Conservation of Key Structural Features Seen in the Eukaryal gamma-AMPK

In mammals, 5′-AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic serine/threonine kinase subunit (alpha) and two regulatory subunits (beta and gamma). The gamma-subunit senses the intracellular energy status by competitively binding AMP and ATP and is thought to be responsible for allosteric regulation of the whole complex which is thought to exist only in eukaryotes. Interestingly, the crystal structure of the archaeal protein MJ1225 recently solved by Inmaculada Gómez and Iker Oyenarte from the group headed by Alfonso Martínez-Cruz reveals strong conservation of key structural features seen in the eukaryal gamma-AMPK that might indicate the existence of a similar energy sensor in prokaryotes. More importantly, it reveals a non-canonical nucleotide binding site, which had not been previously described in cystathionine β-synthase domains so far. This novel site shows striking similarities with a symmetry-related crevice of the mammalian enzyme that hosts the pathological mutation N488I. The results are published in the last issue of Journal of Molecular Biology.