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Publication Abstract from PubMed

Translation is a tightly regulated process that ensures optimal protein quality and enables adaptation to energy/nutrient availability. The alpha-kinase eukaryotic elongation factor 2 kinase (eEF-2K), a key regulator of translation, specifically phosphorylates the guanosine triphosphatase eEF-2, thereby reducing its affinity for the ribosome and suppressing the elongation phase of protein synthesis. eEF-2K activation requires calmodulin binding and autophosphorylation at the primary stimulatory site, T348. Biochemical studies predict a calmodulin-mediated activation mechanism for eEF-2K distinct from other calmodulin-dependent kinases. Here, we resolve the atomic details of this mechanism through a 2.3-A crystal structure of the heterodimeric complex of calmodulin and the functional core of eEF-2K (eEF-2KTR). This structure, which represents the activated T348-phosphorylated state of eEF-2KTR, highlights an intimate association of the kinase with the calmodulin C-lobe, creating an "activation spine" that connects its amino-terminal calmodulin-targeting motif to its active site through a conserved regulatory element.

Structural basis for the calmodulin-mediated activation of eukaryotic elongation factor 2 kinase.,Piserchio A, Isiorho EA, Long K, Bohanon AL, Kumar EA, Will N, Jeruzalmi D, Dalby KN, Ghose R Sci Adv. 2022 Jul 8;8(27):eabo2039. doi: 10.1126/sciadv.abo2039. Epub 2022 Jul 6. PMID:35857468^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.