2lx4: Difference between revisions
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==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=''> | |||
== 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> | |||
</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://www.rcsb.org/pdb/explore.do?structureId=2lx4 RCSB], [http://www.ebi.ac.uk/pdbsum/2lx4 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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> | |||
[[Category: Dip, P | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
[[Category: Gruber, G | </div> | ||
[[Category: Marshansky, V | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Dip, P]] | |||
[[Category: Gruber, G]] | |||
[[Category: Marshansky, V]] | |||
[[Category: Alpha helix]] | [[Category: Alpha helix]] | ||
[[Category: Ph sensor]] | [[Category: Ph sensor]] | ||
