4JVP

Three dimensional structure of broadly neutralizing anti - Hepatitis C virus (HCV) glycoprotein E2 alpaca nanobody D03

Summary for 4JVP

• Entry DOI: 10.2210/pdb4jvp/pdb
• Descriptor: Anti-HCV E2 alpaca nanobody D03, SULFATE ION (3 entities in total)
• Functional Keywords: heavy-chain antibody, nanobody, immunoglobulin fold, antibody, immune system
• Biological source: Vicugna pacos (alpaca)
• Total number of polymer chains: 2
• Total formula weight: 32087.08

Authors

Krey, T.,Rey, F.A. (deposition date: 2013-03-26, release date: 2013-04-24, Last modification date: 2024-11-20)

Primary citation

Tarr, A.W.,Lafaye, P.,Meredith, L.,Damier-Piolle, L.,Urbanowicz, R.A.,Meola, A.,Jestin, J.L.,Brown, R.J.,McKeating, J.A.,Rey, F.A.,Ball, J.K.,Krey, T.
An alpaca nanobody inhibits hepatitis C virus entry and cell-to-cell transmission.
Hepatology, 58:932-939, 2013

PubMed Abstract: Severe liver disease caused by chronic hepatitis C virus is the major indication for liver transplantation. Despite recent advances in antiviral therapy, drug toxicity and unwanted side effects render effective treatment in liver-transplanted patients a challenging task. Virus-specific therapeutic antibodies are generally safe and well-tolerated, but their potential in preventing and treating hepatitis C virus (HCV) infection has not yet been realized due to a variety of issues, not least high production costs and virus variability. Heavy-chain antibodies or nanobodies, produced by camelids, represent an exciting antiviral approach; they can target novel highly conserved epitopes that are inaccessible to normal antibodies, and they are also easy to manipulate and produce. We isolated four distinct nanobodies from a phage-display library generated from an alpaca immunized with HCV E2 glycoprotein. One of them, nanobody D03, recognized a novel epitope overlapping with the epitopes of several broadly neutralizing human monoclonal antibodies. Its crystal structure revealed a long complementarity determining region (CD3) folding over part of the framework that, in conventional antibodies, forms the interface between heavy and light chain. D03 neutralized a panel of retroviral particles pseudotyped with HCV glycoproteins from six genotypes and authentic cell culture-derived particles by interfering with the E2-CD81 interaction. In contrast to some of the most broadly neutralizing human anti-E2 monoclonal antibodies, D03 efficiently inhibited HCV cell-to-cell transmission.

PubMed: 23553604
DOI: 10.1002/hep.26430

Experimental method

X-RAY DIFFRACTION (1.76 Å)