Ill be darn....LOL Whooda Thunk it? FRANCE IS NOT GOING TO CUT THEM ANY SLACK!!! Viruses. 2014 Mar 11;6(3):1149-87. doi: 10.3390/v6031149. Incorporation of hepatitis C virus e1 and e2 glycoproteins: the keystones on a peculiar virion. Vieyres G1, Dubuisson J2, Pietschmann T3. -- So far, both the crystal structure of the HCV glycoprotein complex and the 3D reconstruction of the virion are missing. The heterogeneity of the virions, the difficult to purify them and their resemblance to VLDL limit the resolution and precision of structural information obtained by cryoelectron microscopy [14–16] (see Section 3.1). Efforts to crystallize E1 and E2 have also met several challenges inherent to the biology of the glycoproteins, including the presence of transmembrane domains, of a dense glycan shield and the necessary cooperation between E1 and E2 for their folding. In the absence of crystallographic data, related viral glycoproteins served as a scaffold to build homology-based structural models. Briefly, E1 or E2 protein sequence was aligned to the envelope protein of closely related viruses with a known structure, typically their fusion protein. However, in the case of HCV, the identity of the fusion protein remains unknown, so it is not clear which one of E1 or E2 protein should be aligned to the flavivirus E protein for instance. Computational analysis was applied to obtain a 3D model. This model was then further refined to accommodate the experimental data (for instance the exposure of the receptor binding sites, glycosylation sites and antibody epitopes, the heterodimerization surface, putative fusion peptide, and more recently, the disulfide bridge connections [62]). Surprisingly however, both E1 and E2 models have been calculated based on their homology with the same protein, namely the TBEV envelope protein E [63,64]. In both cases, the authors found a homology resulting in the description of either E1 [64] or E2 [63] as a class II fusion protein. Also, the small size of E1 and E2 ectodomains as compared to their flavivirus parent (E ectodomain) is startling. This suggested that HCV might have a truncated class II fusion protein [64,65] or that both glycoproteins might participate in the fusion process, as also suggested by E1E2 mutagenesis and functional fusion assays [29,66–70]. Interestingly, similar analyses successfully predicted the bunyavirus class II fold and fusion loop [71,72]. mdpi/1999-4915/6/3/1149
Posted on: Mon, 17 Mar 2014 05:33:23 +0000
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