Mini ReviewFolding of viral glycoproteins in the endoplasmic reticulum
Introduction
The endoplasmic reticulum (ER) is the site of synthesis and folding of proteins destined for secretion, for the secretory and endocytic organelles and for the plasma membrane. The processes of folding and assembly of newly synthesized polypeptides are assisted and facilitated by molecular chaperones and folding factors present in the ER lumen. Folded proteins become transport-competent, are sorted away from conformational variants of themselves, from ER-resident proteins, from unfolded or unassembled products and are targeted to their final destination. Terminally misfolded products and unassembled subunits of oligomeric complexes are efficiently retained in the ER and eventually degraded by the ER quality control machinery (Ellgaard et al., 1999).
Section snippets
Protein folding in the ER
Folding of proteins in living cells is a complex and error prone process. The lumen of the ER offers to newly synthesized proteins an ideal environment to acquire native, functional structure. A number of resident molecular chaperones and folding factors are present at high concentration. Proteins such as BiP, calnexin, calreticulin, UDP-glucose:glycoprotein glucosyl transferase (GT), GRP94, PDI, ERp57, ERp72 and others, not only assist folding, but also make sure that incompletely folded or
Quality control of proteins in the ER
The association of newly synthesized proteins with the ER-resident factors mentioned above not only provides an essential assistance during the folding process, but it also represents an important mechanism for quality control of gene products at the post-translational level. Association of newly synthesized proteins with molecular chaperones and folding factors consists of on-and-off cycles. Since all the folding factors and molecular chaperones are localized in the ER by retention and
The folding of viral glycoproteins
In the laboratory of Professor Ari Helenius at the Institute of Biochemistry, ETH Zurich, we have investigated the processes of folding of viral glycoproteins expressed in the mammalian ER with particular focus on co-translational events.
Folding of proteins in the ER of mammalian cells starts co-traslationally, i.e. during the synthesis of the polypeptide chain, and is terminated post-translationally. The folding process is assisted by a number of different molecular chaperones and folding
Perspectives
Relevant progresses to elucidate the mechanisms underlying protein (in particular glycoprotein) folding and quality control in the ER have been done in the last decade (Ellgaard et al., 1999 for a recent review). The challenge for the future is to acquire the capacity to intervene in protein expression, folding, and traffic by modulating cellular quality control. This may prove essential in the treatment of diseases with ER storage etiology or of diseases where cleavage products of proteins
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