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| | ==NMR solution structure of peptide a2N(1-17) from Mus musculus V-ATPase== | | ==NMR solution structure of peptide a2N(1-17) from Mus musculus V-ATPase== |
| - | <StructureSection load='2lx4' size='340' side='right' caption='[[2lx4]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2lx4' size='340' side='right'caption='[[2lx4]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2lx4]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LX4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LX4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2lx4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LX4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LX4 FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2lx4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lx4 OCA], [http://pdbe.org/2lx4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2lx4 RCSB], [http://www.ebi.ac.uk/pdbsum/2lx4 PDBsum]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2lx4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lx4 OCA], [https://pdbe.org/2lx4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lx4 RCSB], [https://www.ebi.ac.uk/pdbsum/2lx4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lx4 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VPP2_MOUSE VPP2_MOUSE]] Part of the proton channel of V-ATPases (By similarity). Essential component of the endosomal pH-sensing machinery. May play a role in maintaining the Golgi functions, such as glycosylation maturation, by controlling the Golgi pH.<ref>PMID:16415858</ref> | + | [https://www.uniprot.org/uniprot/VPP2_MOUSE VPP2_MOUSE] Part of the proton channel of V-ATPases (By similarity). Essential component of the endosomal pH-sensing machinery. May play a role in maintaining the Golgi functions, such as glycosylation maturation, by controlling the Golgi pH.<ref>PMID:16415858</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Previously, we reported an acidification-dependent interaction of the endosomal V-ATPase with cytohesin-2, a GDP/GTP-exchange factor (GEF), suggesting that it functions as a pH-sensing receptor. Here, we have studied the molecular mechanism of signaling between the V-ATPase, cytohesin-2 and Arf GTP-binding proteins. We found that part of the N-terminal cytosolic tail of the V-ATPase a2-subunit (a2N), corresponding to its first seventeen amino acids (a2N(1-17)), potently modulates the enzymatic GDP/GTP-exchange activity of cytohesin-2. Moreover, this peptide strongly inhibits GEF-activity via direct interaction with the Sec7 domain of cytohesin-2. The structure of a2N(1-17) and its amino acids F(5), M(10) and Q(14) involved in interaction with Sec7 domain were determined by NMR spectroscopy analysis. In silico docking experiments revealed that part of the V-ATPase formed by its a2N(1-17) epitope competes with the Switch 2 region of Arf1 and Arf6 for binding to the Sec7 domain of cytohesin-2. The amino acid sequence alignment and GEF-activity studies also uncovered the conserved character of signaling between all four (a1-a4) a-subunit isoforms of mammalian V-ATPase and cytohesin-2. Moreover, the conserved character of this phenomenon was also confirmed in experiments showing binding of mammalian cytohesin-2 to the intact yeast V-ATPase holo-complex. Thus, here we have uncovered an evolutionarily conserved function of the V-ATPase as a novel cytohesin-signaling receptor.
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| - | The N-terminus of a-Subunit Isoforms is Involved in Signaling between V-ATPase and Cytohesin-2.,Hosokawa H, Dip PV, Merkulova M, Bakulina A, Zhuang Z, Khatri A, Jian X, Keating SM, Bueler SA, Rubinstein JL, Randazzo PA, Ausiello DA, Gruber G, Marshansky V J Biol Chem. 2013 Jan 3. PMID:23288846<ref>PMID:23288846</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 2lx4" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Dip, P]] | + | [[Category: Large Structures]] |
| - | [[Category: Gruber, G]] | + | [[Category: Mus musculus]] |
| - | [[Category: Marshansky, V]] | + | [[Category: Dip P]] |
| - | [[Category: Alpha helix]] | + | [[Category: Gruber G]] |
| - | [[Category: Ph sensor]]
| + | [[Category: Marshansky V]] |
| - | [[Category: Proton transport]]
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| - | [[Category: Sec7 binding motif]]
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| - | [[Category: Subunit some]]
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| - | [[Category: V-atpase]] | + | |
