Signals for the incorporation and orientation of cytochrome P450 in the endoplasmic reticulum membrane

@article{Monier1988SignalsFT,
  title={Signals for the incorporation and orientation of cytochrome P450 in the endoplasmic reticulum membrane},
  author={S. Monier and P. Van Luc and G. Kreibich and D. Sabatini and M. Adesnik},
  journal={The Journal of Cell Biology},
  year={1988},
  volume={107},
  pages={457 - 470}
}
Cytochrome P450b is an integral membrane protein of the rat hepatocyte endoplasmic reticulum (ER) which is cotranslationally inserted into the membrane but remains largely exposed on its cytoplasmic surface. The extreme hydrophobicity of the amino-terminal portion of P450b suggests that it not only serves to initiate the cotranslational insertion of the nascent polypeptide but that it also halts translocation of downstream portions into the lumen of the ER and anchors the mature protein in the… Expand
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The amino-terminal amino acid sequence of cytochrome P-450 synthesized in an mRNA-dependent system resembles in hydrophobicity the signal segment of presecretory proteins and therefore may serve to insert the polypeptide into the membrane during synthesis. Expand
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The influenza hemagglutinin insertion signal is not cleaved and does not halt translocation when presented to the endoplasmic reticulum membrane as part of a translocating polypeptide
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The finding that the interiorized signal did not halt translocation of downstream sequences, even though it contains a hydrophobic region and must enter the membrane in the same configuration as natural stop-transfer signals, indicates that the HA insertion signal lacks essential elements of halt transfer signals that makes the latter effective membrane-anchoring domains. Expand
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It is concluded that a short amino‐terminal segment of the cytochrome P‐450 functions not only as an insertion signal but also as a stop‐transfer sequence, similar to the internal signal of type II plasma membrane proteins, but differs from the latter in the topogenic function. Expand
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It is postulated that co-translational insertion of P-450(1) into microsomal membranes requires SRP and possesses an uncleavable signal sequence that can be recognized by SRP, a known component of the membrane translocation machinery for secretory proteins. Expand
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The hydrophobic NH2 terminus of NA, although capable of providing the signal function in translocation across the rough endoplasmic reticulum, interferes with the transport of the chimeric HA to the cell surface. Expand
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