Doing Double Duty

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Science  28 Jun 2002:
Vol. 296, Issue 5577, pp. 2301
DOI: 10.1126/science.296.5577.2301b

For a membrane protein, achieving the proper topological arrangement generally relies on two encoded domains. An NH2-terminal signal sequence helps to attach the protein synthesis machinery to the translocation pore in the target membrane; in many cases, this leader sequence of about 10 residues is later cleaved and discarded. Second, a transmembrane region of about 20 to 25 residues contains hydrophobic amino acids that fix the protein within the lipid bilayer. Cocquerel et al. describe how hepatitis C virus has combined these domains into one segment for its envelope proteins E1 and E2, which are made as a single unit. The signal sequence of E2 overlaps almost completely with the last half of the transmembrane region of E1. Thus, after the E2 signal sequence passes into the pore, pulling the remainder of the E2 protein with it, a protease cuts them apart. Acting then as the transmembrane anchor, the former signal sequence triggers a conformational change in the pore that results in release of the COOH-terminal portion of E1 sideways into the lipid bilayer. How this release occurs awaits structural characterization of the intermediates. — GJC

EMBO J.21, 2893 (2002).

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