Pause transfer: a topogenic sequence in apolipoprotein B mediates stopping and restarting of translocation

SL Chuck, VR Lingappa - Cell, 1992 - cell.com
SL Chuck, VR Lingappa
Cell, 1992cell.com
Previously, we described the stepwise translocation of a large amino-terminal fragment of
apolipoprotein B (apo 815) in which the nascent secretory chain translocates through a
series of distinct, nonintegrated transmembrane intermediates with large domains exposed
to the cytoplasm. Thus, apo 815 appears to stop and restart translocation at several points.
We have identified a sequence of amino acids in apo B15 that confers this behavior on a
heterologous chimeric protein. In addition, we dissect pausing into two distinct steps …
Summary
Previously, we described the stepwise translocation of a large amino-terminal fragment of apolipoprotein B (apo 815) in which the nascent secretory chain translocates through a series of distinct, nonintegrated transmembrane intermediates with large domains exposed to the cytoplasm. Thus, apo 815 appears to stop and restart translocation at several points. We have identified a sequence of amino acids in apo B15 that confers this behavior on a heterologous chimeric protein. In addition, we dissect pausing into two distinct steps, stopping and restarting, thereby trapping otherwise transient intermediates. Finally, we demonstrate the function of a second “pause transfer” sequence over 200 amino acids downstream in apo B15 that restarts translocation posttranslationally, suggesting that multiple pause transfer sequences are involved in the biogenesis of apolipoprotein B.
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