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Journal of Virology, April 2000, p. 3623-3633, Vol. 74, No. 8
CNRS-UMR8526, IBL/Institut Pasteur de Lille,
59021 Lille Cedex,1 and CNRS-UPR412,
IBCP, 69367 Lyon Cedex 07,2 France
Received 25 June 1999/Accepted 24 January 2000
For most membrane proteins, the transmembrane domain (TMD) is more
than just an anchor to the membrane. The TMDs of hepatitis C virus
(HCV) envelope proteins E1 and E2 are extreme examples of the
multifunctionality of such membrane-spanning sequences. Indeed, they
possess a signal sequence function in their C-terminal half, play a
major role in endoplasmic reticulum localization of E1 and E2, and are
potentially involved in the assembly of these envelope proteins. These
multiple functions are supposed to be essential for the formation of
the viral envelope. As for the other viruses of the family
Flaviviridae, these anchor domains are composed of two
stretches of hydrophobic residues separated by a short segment
containing at least one fully conserved charged residue. Replacement of
these charged residues by an alanine in HCV envelope proteins led to an
alteration of all of the functions performed by their TMDs, indicating
that these functions are tightly linked together. These data suggest
that the charged residues of the TMDs of HCV glycoproteins play a key
role in the formation of the viral envelope.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Charged Residues in the Transmembrane Domains of
Hepatitis C Virus Glycoproteins Play a Major Role in the Processing,
Subcellular Localization, and Assembly of These Envelope
Proteins
*
Corresponding author. Mailing address: Equipe
Hépatite C, CNRS-UMR8526, Institut de Biologie de Lille & Institut Pasteur de Lille, 1 rue Calmette, BP447, 59021 Lille Cedex,
France. Phone: (33) 3 20 87 11 60. Fax: (33) 3 20 87 11 11. E-mail:
jean.dubuisson{at}ibl.fr.
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