5J8H

Structure of calmodulin in a complex with a peptide derived from a calmodulin-dependent kinase

Summary for 5J8H

• Entry DOI: 10.2210/pdb5j8h/pdb
• NMR Information: BMRB: 30063
• Descriptor: Calmodulin, Eukaryotic elongation factor 2 kinase, CALCIUM ION (3 entities in total)
• Functional Keywords: calmodulin eef2k complex kinase, metal binding protein-transferase complex, metal binding protein/transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 19969.12

Authors

Alphonse, S.,Lee, K.,Piserchio, A.,Tavares, C.D.J.,Giles, D.H.,Wellmann, R.M.,Dalby, K.N.,Ghose, R. (deposition date: 2016-04-07, release date: 2016-09-07, Last modification date: 2024-05-15)

Primary citation

Lee, K.,Alphonse, S.,Piserchio, A.,Tavares, C.D.,Giles, D.H.,Wellmann, R.M.,Dalby, K.N.,Ghose, R.
Structural Basis for the Recognition of Eukaryotic Elongation Factor 2 Kinase by Calmodulin.
Structure, 24:1441-1451, 2016

PubMed Abstract: Binding of Ca(2+)-loaded calmodulin (CaM) activates eukaryotic elongation factor 2 kinase (eEF-2K) that phosphorylates eEF-2, its only known cellular target, leading to a decrease in global protein synthesis. Here, using an eEF-2K-derived peptide (eEF-2KCBD) that encodes the region necessary for its CaM-mediated activation, we provide a structural basis for their interaction. The striking feature of this association is the absence of Ca(2+) from the CaM C-lobe sites, even under high Ca(2+) conditions. eEF-2KCBD engages CaM largely through the C lobe of the latter in an anti-parallel 1-5-8 hydrophobic mode reinforced by a pair of unique electrostatic contacts. Sparse interactions of eEF-2KCBD with the CaM N lobe results in persisting inter-lobe mobility. A conserved eEF-2K residue (W85) anchors it to CaM by inserting into a deep hydrophobic cavity within the CaM C lobe. Mutation of this residue (W85S) substantially weakens interactions between full-length eEF-2K and CaM in vitro and reduces eEF-2 phosphorylation in cells.

PubMed: 27499441
DOI: 10.1016/j.str.2016.06.015

Experimental method

SOLUTION NMR