3ikk

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{{Seed}}
 
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[[Image:3ikk.jpg|left|200px]]
 
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==Crystal structure analysis of msp domain==
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The line below this paragraph, containing "STRUCTURE_3ikk", creates the "Structure Box" on the page.
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<StructureSection load='3ikk' size='340' side='right'caption='[[3ikk]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3ikk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IKK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IKK FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.5&#8491;</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=3ikk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ikk OCA], [https://pdbe.org/3ikk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ikk RCSB], [https://www.ebi.ac.uk/pdbsum/3ikk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ikk ProSAT]</span></td></tr>
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{{STRUCTURE_3ikk| PDB=3ikk | SCENE= }}
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/VAPB_HUMAN VAPB_HUMAN] Adult-onset proximal spinal muscular atrophy, autosomal dominant;Amyotrophic lateral sclerosis. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
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== Function ==
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[https://www.uniprot.org/uniprot/VAPB_HUMAN VAPB_HUMAN] Participates in the endoplasmic reticulum unfolded protein response (UPR) by inducing ERN1/IRE1 activity. Involved in cellular calcium homeostasis regulation.<ref>PMID:16891305</ref> <ref>PMID:20940299</ref> <ref>PMID:22131369</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/ik/3ikk_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3ikk 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 Pro56Ser mutation in the human VAPB MSP domain causes a familial amyotrophic lateral sclerosis. Here we present the first structural investigation of both wild-type and Pro56Ser mutant MSP domains. The results reveal that the wild-type MSP domain is well-folded at neutral pH but can undergo acid-induced unfolding reversibly. It has a thermodynamic stability energy (DeltaG degrees (N-U)) of 7.40 kcal/mol and is also active in binding to a Nir2 peptide with a K(D) of 0.65 muM. Further determination of its crystal structure reveals that it adopts a seven-strand immunoglobulin-like beta sandwich in which Pro56 adopts the unusual cis-peptide bond conformation that appears to be critical in maintaining the characteristic S-shaped loop. Markedly, the Pro56Ser mutation renders the MSP domain insoluble in buffer. Nevertheless, as facilitated by our recent discovery that "insoluble proteins" can be solubilized in salt-free water, we have successfully characterized the residue-specific conformation of the Pro56Ser mutant by CD and heteronuclear NMR spectroscopy. The Pro56Ser mutant remains lacking of the native tight packing and secondary structures under various conditions and was further characterized as having a non-native helical conformation weakly populated at pH 3.5. Intriguingly, Pro12 located in another S-shaped loop also adopts the cis-peptide bond conformation, and its mutation to Ser is able to make the MSP domain highly insoluble and unfolded like the Pro56Ser mutant. Our study thus implies that the Pro56Ser mutation might lead to ALS by eliminating the native MSP structure, which consequently leads to aggregation and loss of functions under physiological conditions.
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===Crystal structure analysis of msp domain===
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Elimination of the native structure and solubility of the hVAPB MSP domain by the Pro56Ser mutation that causes amyotrophic lateral sclerosis.,Shi J, Lua S, Tong JS, Song J Biochemistry. 2010 May 11;49(18):3887-97. PMID:20377183<ref>PMID:20377183</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3ikk" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_20377183}}, adds the Publication Abstract to the page
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*[[Vesicle-associated membrane protein 3D structures|Vesicle-associated membrane protein 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 20377183 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_20377183}}
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__TOC__
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</StructureSection>
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==About this Structure==
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3IKK is a 2 chains structure with sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IKK OCA].
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==Reference==
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<ref group="xtra">PMID:20377183</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Lua, S.]]
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[[Category: Large Structures]]
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[[Category: Shi, J.]]
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[[Category: Lua S]]
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[[Category: Song, J.]]
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[[Category: Shi J]]
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[[Category: Alternative splicing]]
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[[Category: Song J]]
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[[Category: Amyotrophic lateral sclerosis]]
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[[Category: Cell membrane]]
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[[Category: Coiled coil]]
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[[Category: Disease mutation]]
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[[Category: Host-virus interaction]]
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[[Category: Membrane]]
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[[Category: Membrane protein]]
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[[Category: Neurodegeneration]]
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[[Category: Phosphoprotein]]
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[[Category: Transmembrane]]
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[[Category: Vapb msp]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 26 08:31:37 2010''
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Current revision

Crystal structure analysis of msp domain

PDB ID 3ikk

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