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Membrane‐bound peptides from V‐ATPase subunit a do not interact with an indole‐type inhibitor
Author(s) -
Hesselink Renske W.,
Fedorov Alexander,
Hemminga Marcus A.,
Prieto Manuel
Publication year - 2008
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.980
Subject(s) - peptide , chemistry , atpase , membrane , transmembrane protein , biochemistry , transmembrane domain , v atpase , indole test , biophysics , protein subunit , membrane biology , electrochemical gradient , arginine , enzyme , biology , amino acid , receptor , gene
The V‐ATPases are ATP‐dependent proton pumps, found in virtually all cells, responsible for acidification of organelles and energizing of plasma membranes. Its role in diseases, such as osteoporosis and metastatic cancer, makes the V‐ATPase a potential drug target. Short synthetic peptides that are presented here mimic the 7th transmembrane domain (TM7) of subunit a (Vph1p) of Saccharomyces cerevisiae V‐ATPase, an essential part of the membrane‐bound V O domain, where proton translocation takes place. The peptides adopt a transmembrane configuration only in membranes containing anionic lipids, stressing the importance of strong interfacial anchoring by the flanking lysines. Peptide P1, which contains the essential arginine R735, is monomeric, whereas peptide P2, which lacks this extra charge, tends to aggregate in the membrane. SB 242784, which is a highly potent inhibitor of V‐ATPase, does not show any interaction with the peptides, indicating that TM7 alone is not sufficient for inhibitor binding. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.