A New Mode of Dimerization of Allosteric Enzymes with ACT Domains Revealed by the Crystal Structure of the Aspartate Kinase from Cyanobacteria |
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Authors: | Adeline Y Robin David Cobessi Gilles Curien Mylène Robert-Genthon Jean-Luc Ferrer Renaud Dumas |
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Institution: | 1 Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5168, Grenoble, France 2 Commissariat à l'Énergie Atomique, Direction des Sciences du Vivant, Institut de Recherches en Technologies et Sciences pour le Vivant, Laboratoire de Physiologie Cellulaire Végétale, Grenoble, France 3 Université Joseph Fourier, Grenoble, France 4 Institut National de la Recherche Agronomique, Unité Mixte de Recherche 1200, Grenoble, France 5 Institut de Biologie Structurale J.-P. Ebel, Commissariat à l'Énergie Atomique/Centre National de la Recherche Scientifique/Université Joseph Fourier, Groupe Synchrotron, Grenoble, France |
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Abstract: | Aspartate kinases (AKs) can be divided in two subhomology divisions, AKα and AKβ, depending on the presence of an extra sequence of about 60 amino acids, which is found only in the N-terminus of all AKα's. To date, the structures of AKα failed to provide a role for this additional N-terminal sequence. In this study, the structure of the AKβ from the Cyanobacteria Synechocystis reveals that this supplementary sequence is linked to the dimerization mode of AKs. Its absence in AKβ leads to the dimerization by the catalytic domain instead of involving the ACT domains Pfam 01842; small regulatory domains initially found in AK, chorismate mutase and TyrA (prephenate dehydrogenase)] as observed in AKα. Thus, the structural analysis of the Synechocystis AKβ revealed a dimer with a novel architecture. The four ACT domains of each monomer interact together and do not make any contact with those of the second monomer. The enzyme is inhibited synergistically by threonine and lysine with the binding of threonine first. The interaction between ACT1 and ACT4 or between ACT2 and ACT3 generates a threonine binding site and a lysine binding site at each interface, making a total of eight regulatory sites per dimer and allowing a fine-tuning of the AK activity by the end products, threonine and lysine. |
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Keywords: | AK aspartate kinase ACT domain small regulatory domain initially found in AK chorismate mutase and TyrA (prephenate dehydrogenase) UK uridylate kinase AKsyn/AKath/AKeco/AKmja/AKcgl/AKtth aspartate kinase from Synechocystis/Arabidopsis thaliana/Escherichia coli/Methanococcus jannaschii/Corynebacterium glutamicum/Thermus thermophilus SAM S-adenosylmethionine |
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