FIG 9.

Structural context of mutations occurring in domain I of NS5A and NS5B protein of H77S.2 virus during persistent infection of chimpanzee 4x0193. (A) NS5A residues involved in mutations are highlighted in yellow on the surface of domain I of the protein from the genotype 1b Con1 strain of HCV (PDB entry 3FQQ) (left). Residues with key roles in homodimer formation are highlighted in green (32). Also shown is an imposition of the monomer structures proposed in alternate structural models (right), with the peptide backbone from PDB entry 2FQQ (32) shown in gray and that from PDB entry 1ZH1 (33) in cyan. The side chain of K68 is highlighted in yellow in both structures. Side chains of residues presumed to be closest to the membrane surface in PDB entry 1ZH1 (33) are shown as stick models. The structural superposition was calculated using the jCE/jFATCAT Structure Alignment Server v2.6 (http://source.rcsb.org/jfatcatserver/index.jsp) with jCE algorithm, PDB entry 3FQQ chain A, and 1ZH1 chain A. (B) Residues involved in nonsynonymous mutations in the NS5B protein are highlighted in a structural model of the polymerase from wild-type H77c virus (PDB entry 2XI2). Residues are labeled and colored as described in the legend to Fig. 8.