Please use this identifier to cite or link to this item:
https://hdl.handle.net/10356/99231
Title: | The N termini of a-subunit isoforms are involved in signaling between vacuolar H+-ATPase (V-ATPase) and cytohesin-2 | Authors: | Dip, Phat Vinh Grüber, Gerhard Marshansky, Vladimir Hosokawa, H. Merkulova, M. Bakulina, A. Zhuang, Z. Khatri, A. Jian, X. Keating, S. M. Bueler, S. A. Rubinstein, J. L. Randazzo, P. A. Ausiello, D. A. |
Keywords: | DRNTU::Science::Biological sciences | Issue Date: | 2013 | Source: | Hosokawa, H., Dip, P. V., Merkulova, M., Bakulina, A., Zhuang, Z., Khatri, A., et al. (2013). The N termini of a-subunit isoforms are involved in signaling between vacuolar H+-ATPase (V-ATPase) and cytohesin-2. Journal of biological chemistry, 288(8), 5896-5913. | Series/Report no.: | Journal of biological chemistry | Abstract: | Previously, we reported an acidification-dependent interaction of the endosomal vacuolar H+-ATPase (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 17 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 Phe5, Met10, and Gln14 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. | URI: | https://hdl.handle.net/10356/99231 http://hdl.handle.net/10220/17563 |
DOI: | 10.1074/jbc.M112.409169 | Schools: | School of Biological Sciences | Fulltext Permission: | none | Fulltext Availability: | No Fulltext |
Appears in Collections: | SBS Journal Articles |
SCOPUSTM
Citations
10
34
Updated on Mar 24, 2024
Web of ScienceTM
Citations
10
37
Updated on Oct 26, 2023
Page view(s) 20
737
Updated on Mar 28, 2024
Google ScholarTM
Check
Altmetric
Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.