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Topological changes in the transmembrane domains of hepatitis C virus envelope glycoproteins
Author(s) -
Cocquerel Laurence,
Op de Beeck Anne,
Lambot Michel,
Roussel Juliette,
Delgrange David,
Pillez André,
Wychowski Czeslaw,
Penin François,
Dubuisson Jean
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf295
Subject(s) - biology , glycoprotein , virology , transmembrane protein , envelope (radar) , membrane topology , virus , transmembrane domain , viral envelope , topology (electrical circuits) , microbiology and biotechnology , genetics , gene , combinatorics , receptor , telecommunications , radar , mathematics , computer science
Hepatitis C virus proteins are synthesized as a polyprotein cleaved by a signal peptidase and viral proteases. The behaviour of internal signal sequences at the C‐terminus of the transmembrane domains of hepatitis C virus envelope proteins E1 and E2 is essential for the topology of downstream polypeptides. We determined the topology of these transmembrane domains before and after signal sequence cleavage by tagging E1 and E2 with epitopes and by analysing their accessibility in selectively permeabilized cells. We showed that, after cleavage by signal peptidase in the endoplasmic reticulum, the C‐terminal orientation of these transmembrane domains changed from luminal to cytosolic. The dynamic behaviour of these transmembrane domains is unique and it is linked to their multifunctionality. By reorienting their C‐terminus toward the cytosol and being part of a transmembrane domain, the signal sequences at the C‐terminus of E1 and E2 contribute to new functions: (i) membrane anchoring; (ii) E1E2 heterodimerization; and (iii) endoplasmic reticulum retention.