Evidence for an alternate model of human P-glycoprotein structure and biogenesis

W. R. Skach, M. C. Calayag, V. R. Lingappa

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

We have studied the transmembrane topology of human P-glycoprotein (MDR1) using protein chimeras in Xenopus oocytes and full-length native protein in a cell-free translation system. We find both in vivo and in vitro, that the peptide region between putative transmembrane helices (TM) 8 and 9 resides in the endoplasmic reticulum lumen not in the cytosol as predicted. The topology of the carboxyl-terminal half of MDR1 therefore appears distinct from the homologous amino-terminal half in which the corresponding region between TM2 and TM3 is cytosolic. Thus, topogenic sequences encoded in the homologous amino and carboxyl domains of MDR1 direct fundamentally different events in biogenesis of the two halves of MDR1. We conclude that the transmembrane topology of MDR1, an important member of the ATP binding cassette (ABC) transporter superfamily, is not as predicted and should be revised.

Original languageEnglish (US)
Pages (from-to)6903-6908
Number of pages6
JournalJournal of Biological Chemistry
Volume268
Issue number10
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Skach, W. R., Calayag, M. C., & Lingappa, V. R. (1993). Evidence for an alternate model of human P-glycoprotein structure and biogenesis. Journal of Biological Chemistry, 268(10), 6903-6908.