1mxe

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spinqualitylabelsall models 1mxe, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Structure of the Complex of Calmodulin with the Target Sequence of CaMKI

Overview

Calcium-saturated calmodulin (CaM) directly activates CaM-dependent, protein kinase I (CaMKI) by binding to a region in the C-terminal, regulatory sequence of the enzyme to relieve autoinhibition. The structure, of CaM in a high-affinity complex with a 25-residue peptide of CaMKI, (residues 294-318) has been determined by X-ray crystallography at 1.7 A, resolution. Upon complex formation, the CaMKI peptide adopts an, alpha-helical conformation, while changes in the CaM domain linker enable, both its N- and C-domains to wrap around the peptide helix. Target peptide, residues Trp-303 (interacting with the CaM C-domain) and Met-316 (with the, CaM N-domain) define the mode of binding as 1-14. In addition, two basic, patches on the peptide form complementary charge interactions with CaM., The CaM-peptide affinity is approximately 1 pM, compared with 30 nM for, the CaM-kinase complex, indicating that activation of autoinhibited CaMKI, by CaM requires a costly energetic disruption of the interactions between, the CaM-binding sequence and the rest of the enzyme. We present, biochemical and structural evidence indicating the involvement of both CaM, domains in the activation process: while the C-domain exhibits tight, binding toward the regulatory sequence, the N-domain is necessary for, activation. Our crystal structure also enables us to identify the full, CaM-binding sequence. Residues Lys-296 and Phe-298 from the target peptide, interact directly with CaM, demonstrating overlap between the, autoinhibitory and CaM-binding sequences. Thus, the kinase activation, mechanism involves the binding of CaM to residues associated with the, inhibitory pseudosubstrate sequence.

About this Structure

1MXE is a Protein complex structure of sequences from Drosophila melanogaster with CA as ligand. Active as Calcium/calmodulin-dependent protein kinase, with EC number 2.7.11.17 Full crystallographic information is available from OCA.

Reference

Structure of the complex of calmodulin with the target sequence of calmodulin-dependent protein kinase I: studies of the kinase activation mechanism., Clapperton JA, Martin SR, Smerdon SJ, Gamblin SJ, Bayley PM, Biochemistry. 2002 Dec 17;41(50):14669-79. PMID:12475216

Page seeded by OCA on Tue Nov 20 21:46:55 2007