2lx4
From Proteopedia
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== Function == | == Function == | ||
[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> | [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> | ||
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| - | == 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. | ||
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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 class="pdbe-citations 2lx4" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
NMR solution structure of peptide a2N(1-17) from Mus musculus V-ATPase
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