Protein translocation: Tunnel vision

  • Matlack K
  • Mothes W
  • Rapoport T
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Protein transport across the endoplasmic reticulum (ER) membrane in eukaryotes and across the cytoplasmic membrane in prokaryotes is a decisive step in the biosynthesis of most secretory proteins. Transport occurs through a hydrophilic channel (Simon and Blobel, 1991; Crowley et al., 1993) that is evolutionarily ancient and part of a protein translocation machine. This channel not only translocates secretory proteins but also integrates membrane proteins into the lipid bilayer. To accomplish these tasks it must perform and coordinate a large number of different functions. It must identify the signal sequences of its substrates, open in response to them, transport the substrate from one side of the membrane to the other, and finally close, all without allowing anything but the translocation substrate to pass. In the case of membrane proteins, which can have a wide variety of topologies, some parts must be translocated across the membrane while others must be left in the cytoplasm. Those hydrophobic segments that will ultimately reside within the membrane must be recognized, oriented with respect to the plane of the membrane, and released out the side of the channel into the lipid, a sequence of events that may have to be repeated multiple times during the integration of a single membrane protein. The size and wide variety of the substrates with which this channel must interact, as well as the ability of its walls to open toward the lipid, distinguish it from many other channels and must require of it great structural flexibility.

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  • Kent E.S. Matlack

  • Walther Mothes

  • Tom A. Rapoport

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