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[[Image:1mxe.gif|left|200px]]<br /><applet load="1mxe" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1mxe, resolution 1.70&Aring;" />
'''Structure of the Complex of Calmodulin with the Target Sequence of CaMKI'''<br />


==Overview==
==Structure of the Complex of Calmodulin with the Target Sequence of CaMKI==
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.
<StructureSection load='1mxe' size='340' side='right'caption='[[1mxe]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1mxe]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MXE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MXE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1mxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mxe OCA], [https://pdbe.org/1mxe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mxe RCSB], [https://www.ebi.ac.uk/pdbsum/1mxe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mxe ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CALM_DROME CALM_DROME] Calmodulin mediates the control of a large number of enzymes, ion channels and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mx/1mxe_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1mxe ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1MXE is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] with <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Calcium/calmodulin-dependent_protein_kinase Calcium/calmodulin-dependent protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.17 2.7.11.17] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MXE OCA].
*[[Calmodulin 3D structures|Calmodulin 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12475216 12475216]
[[Category: Calcium/calmodulin-dependent protein kinase]]
[[Category: Drosophila melanogaster]]
[[Category: Drosophila melanogaster]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Bayley, P M.]]
[[Category: Rattus norvegicus]]
[[Category: Clapperton, J A.]]
[[Category: Bayley PM]]
[[Category: Gamblin, S J.]]
[[Category: Clapperton JA]]
[[Category: Martin, S R.]]
[[Category: Gamblin SJ]]
[[Category: Smerdon, S J.]]
[[Category: Martin SR]]
[[Category: CA]]
[[Category: Smerdon SJ]]
[[Category: calmodulin]]
[[Category: calmodulin-pepide complex]]
[[Category: camki]]
[[Category: xray]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:00:02 2008''
Retrieved from "https://proteopedia.org/1mxe"