1w15

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[[Image:1w15.gif|left|200px]]<br />
 
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<applet load="1w15" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1w15, resolution 1.93&Aring;" />
 
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'''RAT SYNAPTOTAGMIN 4 C2B DOMAIN IN THE PRESENCE OF CALCIUM'''<br />
 
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==Overview==
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==rat synaptotagmin 4 C2B domain in the presence of calcium==
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The neuronal protein synaptotagmin 1 functions as a Ca(2+) sensor in, exocytosis via two Ca(2+)-binding C(2) domains. The very similar, synaptotagmin 4, which includes all the predicted Ca(2+)-binding residues, in the C(2)B domain but not in the C(2)A domain, is also thought to, function as a neuronal Ca(2+) sensor. Here we show that, unexpectedly, both C(2) domains of fly synaptotagmin 4 exhibit Ca(2+)-dependent, phospholipid binding, whereas neither C(2) domain of rat synaptotagmin 4, binds Ca(2+) or phospholipids efficiently. Crystallography reveals that, changes in the orientations of critical Ca(2+) ligands, and perhaps their, flexibility, render the rat synaptotagmin 4 C(2)B domain unable to form, full Ca(2+)-binding sites. These results indicate that synaptotagmin 4 is, a Ca(2+) sensor in the fly but not in the rat, that the Ca(2+)-binding, properties of C(2) domains cannot be reliably predicted from sequence, analyses, and that proteins clearly identified as orthologs may, nevertheless have markedly different functional properties.
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<StructureSection load='1w15' size='340' side='right'caption='[[1w15]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1w15]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W15 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W15 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.93&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1w15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w15 OCA], [https://pdbe.org/1w15 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w15 RCSB], [https://www.ebi.ac.uk/pdbsum/1w15 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w15 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SYT4_RAT SYT4_RAT] Synaptotagmin family member which does not bind Ca(2+) (PubMed:7993622). Involved in neuronal dense core vesicles (DCVs) mobility through its interaction with KIF1A. Upon increased neuronal activity, phosphorylation by MAPK8/JNK1 destabilizes the interaction with KIF1A and captures DCVs to synapses (PubMed:29166604). Plays a role in dendrite formation by melanocytes (By similarity).[UniProtKB:Q9H2B2]<ref>PMID:29166604</ref> <ref>PMID:7993622</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w1/1w15_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1w15 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The neuronal protein synaptotagmin 1 functions as a Ca(2+) sensor in exocytosis via two Ca(2+)-binding C(2) domains. The very similar synaptotagmin 4, which includes all the predicted Ca(2+)-binding residues in the C(2)B domain but not in the C(2)A domain, is also thought to function as a neuronal Ca(2+) sensor. Here we show that, unexpectedly, both C(2) domains of fly synaptotagmin 4 exhibit Ca(2+)-dependent phospholipid binding, whereas neither C(2) domain of rat synaptotagmin 4 binds Ca(2+) or phospholipids efficiently. Crystallography reveals that changes in the orientations of critical Ca(2+) ligands, and perhaps their flexibility, render the rat synaptotagmin 4 C(2)B domain unable to form full Ca(2+)-binding sites. These results indicate that synaptotagmin 4 is a Ca(2+) sensor in the fly but not in the rat, that the Ca(2+)-binding properties of C(2) domains cannot be reliably predicted from sequence analyses, and that proteins clearly identified as orthologs may nevertheless have markedly different functional properties.
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==About this Structure==
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Structural basis for the evolutionary inactivation of Ca2+ binding to synaptotagmin 4.,Dai H, Shin OH, Machius M, Tomchick DR, Sudhof TC, Rizo J Nat Struct Mol Biol. 2004 Sep;11(9):844-9. Epub 2004 Aug 15. PMID:15311271<ref>PMID:15311271</ref>
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1W15 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with CA, NA and CL as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1W15 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Structural basis for the evolutionary inactivation of Ca2+ binding to synaptotagmin 4., Dai H, Shin OH, Machius M, Tomchick DR, Sudhof TC, Rizo J, Nat Struct Mol Biol. 2004 Sep;11(9):844-9. Epub 2004 Aug 15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15311271 15311271]
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</div>
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[[Category: Rattus norvegicus]]
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<div class="pdbe-citations 1w15" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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[[Category: Dai, H.]]
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[[Category: Machius, M.]]
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[[Category: Rizo, J.]]
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[[Category: Shin, O.H.]]
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[[Category: Sudhof, T.C.]]
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[[Category: Tomchick, D.R.]]
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[[Category: CA]]
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[[Category: CL]]
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[[Category: NA]]
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[[Category: calcium]]
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[[Category: endocytosis/exocytosis]]
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[[Category: neurotransmitter release]]
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[[Category: synaptotagmin]]
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[[Category: transmembrane]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 17:21:57 2007''
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==See Also==
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*[[Synaptotagmin 3D structures|Synaptotagmin 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Rattus norvegicus]]
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[[Category: Dai H]]
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[[Category: Machius M]]
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[[Category: Rizo J]]
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[[Category: Shin O-H]]
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[[Category: Sudhof TC]]
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[[Category: Tomchick DR]]

Current revision

rat synaptotagmin 4 C2B domain in the presence of calcium

PDB ID 1w15

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