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

William Skach, M. Clara Calayag, Vishwanath R. Lingappa

Research output: Contribution to journalArticle

115 Citations (Scopus)

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 - Apr 5 1993
Externally publishedYes

Fingerprint

P-Glycoprotein
Topology
ATP-Binding Cassette Transporters
Cell-Free System
Xenopus
Endoplasmic Reticulum
Cytosol
Oocytes
Peptides
Proteins
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry

Cite this

Skach, W., 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.

Evidence for an alternate model of human P-glycoprotein structure and biogenesis. / Skach, William; Calayag, M. Clara; Lingappa, Vishwanath R.

In: Journal of Biological Chemistry, Vol. 268, No. 10, 05.04.1993, p. 6903-6908.

Research output: Contribution to journalArticle

Skach, W, Calayag, MC & Lingappa, VR 1993, 'Evidence for an alternate model of human P-glycoprotein structure and biogenesis', Journal of Biological Chemistry, vol. 268, no. 10, pp. 6903-6908.
Skach, William ; Calayag, M. Clara ; Lingappa, Vishwanath R. / Evidence for an alternate model of human P-glycoprotein structure and biogenesis. In: Journal of Biological Chemistry. 1993 ; Vol. 268, No. 10. pp. 6903-6908.
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