CRITICAL AMINO-TERMINAL SEGMENTS IN INSERTION OF RAT-LIVER CYTOCHROME-P450 3A1 INTO THE ENDOPLASMIC-RETICULUM MEMBRANE

Citation
Pja. Vandenbroek et al., CRITICAL AMINO-TERMINAL SEGMENTS IN INSERTION OF RAT-LIVER CYTOCHROME-P450 3A1 INTO THE ENDOPLASMIC-RETICULUM MEMBRANE, Experientia, 52(9), 1996, pp. 851-855
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Multidisciplinary Sciences
Journal title
ISSN journal
0014-4754
Volume
52
Issue
9
Year of publication
1996
Pages
851 - 855
Database
ISI
SICI code
0014-4754(1996)52:9<851:CASIIO>2.0.ZU;2-S
Abstract
An in vitro transcription-translation assay was used to study the memb rane topology of rat liver cytochrome P450 3A1. N-terminus deletion mu tants were constructed to assess the importance of N-terminal regions in the stable incorporation of the protein into the microsomal membran es. Wild-type nascent cytochrome P450 bound to microsomes as an integr al membrane protein through its hydrophobic N-terminal segments, uncle aved by signal peptidase. Deletion of the most N-terminal hydrophobic segment (positions 7-26) had a dramatic effect on endoplasmic reticulu m membrane integration. Confirming the essential role of this stretch in P450 3A1 membrane targeting, proteolysis-resistant membrane-associa ted peptides were observed in all the in vitro translated mutants cont aining that segment. It is concluded that the membrane topogenesis of P450 3A1 is determined mainly by the amino-terminal hydrophobic segmen t.