1mxe
From Proteopedia
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'''Structure of the Complex of Calmodulin with the Target Sequence of CaMKI''' | '''Structure of the Complex of Calmodulin with the Target Sequence of CaMKI''' | ||
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[[Category: Martin, S R.]] | [[Category: Martin, S R.]] | ||
[[Category: Smerdon, S J.]] | [[Category: Smerdon, S J.]] | ||
| - | [[Category: | + | [[Category: Calmodulin]] |
| - | [[Category: | + | [[Category: Calmodulin-pepide complex]] |
| - | [[Category: | + | [[Category: Camki]] |
| - | [[Category: | + | [[Category: Xray]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 01:50:11 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 22:50, 2 May 2008
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. 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 Sat May 3 01:50:11 2008
