Folding of viral envelope glycoproteins in the endoplasmic reticulum

Abstract

Viral glycoproteins fold and oligomerize in the endoplasmic reticulum of the host cell. They employ the cellular machinery and receive assistance from cellular folding factors. During the folding process, they are retained in the compartment and their structural quality is checked by the quality control system of the endoplasmic reticulum. A special characteristic that distinguishes viral fusion proteins from most cellular proteins is the extensive conformational change they undergo during fusion of the viral and cellular membrane. Many viral proteins fold in conjunction with and dependent on a viral partner protein, sometimes even synthesized from the same mRNA. Relevant for folding is that viral glycoproteins from the same or related virus families may consist of overlapping sets of domain modules. The consequences of these features for viral protein folding are at the heart of this review.

Figure 1

Schematic representation of the foolding and the post folding conformational changes of a typical viral fusion protein.

Figure 2

Schematic representation of the folding process for multidomain viral glycoproteins. Different domains are inserted into each other, most likely during virus evolution [3]. The interrupted domain must fold first, which brings the separate polypeptide chains of the next domain close enough to allow its folding. Etcetera.