Membrane-bound peptides from V-ATPase subunit a do not interact with an indole-type inhibitor

R.W. Hesselink, A. Fedorov, M.A. Hemminga, M. Prieto

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)

Abstract

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
Original languageEnglish
Pages (from-to)383-388
JournalJournal of Peptide Science
Volume14
Issue number4
DOIs
Publication statusPublished - 2008

Keywords

  • vacuolar h+-atpase
  • major coat protein
  • proton translocation
  • selective inhibitor
  • concanamycin-a
  • binding-site
  • probes
  • domain

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