TY - JOUR T1 - The Disulfide Bonds in Glycoprotein E2 of Hepatitis C Virus Reveal the Tertiary Organization of the Molecule A1 - Krey, Thomas A1 - d'Alayer, Jacques A1 - Kikuti, Carlos M. A1 - Saulnier, Aure A1 - Damier-Piolle, Laurence A1 - Petitpas, Isabelle A1 - Johansson, Daniel X. A1 - Tawar, Rajiv G. A1 - Baron, Bruno A1 - Robert, Bruno A1 - England, Patrick A1 - Persson, Mats A. A. A1 - Martin, Annette A1 - Rey, FĂ©lix A. Y1 - 2010/02/19 N2 - Author Summary Little is known about the structure of the envelope glycoproteins of the hepatitis C virus (HCV), in spite of their essential role in the viral cycle of this major human pathogen. Here, we determined the connectivity of the 9 disulfide bonds formed by the strictly conserved 18 cysteines of the ectodomain of HCV glycoprotein E2. We show that this information, together with important functional data available in the literature, impose important restrictions to the possible three-dimensional fold of the molecule. Indeed, these constraints allow the unambiguous threading of the predicted secondary structure elements along the polypeptide chain onto the template provided by the crystal structures of related flavi- and alphavirus class II fusion proteins. The resulting model of the tertiary organization of E2 shows the amino acid distribution among the characteristic class II domains, places the CD81 binding site at the interface of domains I and III, and highlights the location of a candidate fusion loop. JF - PLOS Pathogens JA - PLOS Pathogens VL - 6 IS - 2 UR - https://doi.org/10.1371/journal.ppat.1000762 SP - e1000762 EP - PB - Public Library of Science M3 - doi:10.1371/journal.ppat.1000762 ER -