title: HCV E2 core structures and mAbs: something is still missing.
abstract: The lack of structural information on hepatitis C virus (HCV) surface proteins has so far hampered the development of effective vaccines. Recently, two crystallographic structures have described the core portion (E2c) of E2 surface glycoprotein, the primary mediator of HCV entry. Despite the importance of these studies, the E2 overall structure is still unknown and, most importantly, several biochemical and functional studies are in disagreement with E2c structures. Here, the main literature will be discussed and an alternative disulfide bridge pattern will be proposed, based on unpublished human monoclonal antibody reactivity. A modeling strategy aiming at recapitulating the available structural and functional studies of E2 will also be proposed.
authors.affiliation: Laboratory of Microbiology and Virology, Università "Vita-Salute" San Raffaele, Milano, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Castelli
authors.affiliation: Laboratory of Microbiology and Virology, Università "Vita-Salute" San Raffaele, Milano, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Clementi
authors.affiliation: Laboratory of Microbiology and Virology, Università "Vita-Salute" San Raffaele, Milano, Italy.
authors.forename: Giuseppe A
authors.initials: GA
authors.lastname: Sautto
authors.affiliation: Integral Molecular, Philadelphia, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pfaff
authors.affiliation: Integral Molecular, Philadelphia, USA.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Kahle
authors.affiliation: Integral Molecular, Philadelphia, USA.
authors.forename: Trevor
authors.initials: T
authors.lastname: Barnes
authors.affiliation: Integral Molecular, Philadelphia, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Doranz
authors.affiliation: Laboratory for Biomolecular Modeling, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Matteo
authors.initials: M
authors.lastname: Dal Peraro
authors.affiliation: Laboratory of Microbiology and Virology, Università "Vita-Salute" San Raffaele, Milano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Clementi
authors.affiliation: Laboratory of Microbiology and Virology, Università "Vita-Salute" San Raffaele, Milano, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Burioni
authors.affiliation: Laboratory of Microbiology and Virology, Università "Vita-Salute" San Raffaele, Milano, Italy. Electronic address: mancini.nicasio@hsr.it.
authors.forename: Nicasio
authors.initials: N
authors.lastname: Mancini
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D016174:Hepacivirus / Q000472:pathogenicity; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D004220:Disulfides; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus; D003545:Cysteine