4JZO
Three dimensional structure of broadly neutralizing human anti - Hepatitis C virus (HCV) glycoprotein E2 Fab fragment HC84-27
Summary for 4JZO
| Entry DOI | 10.2210/pdb4jzo/pdb |
| Related | 4JZN |
| Descriptor | Anti-HCV E2 Fab HC84-27 heavy chain, Anti-HCV E2 Fab HC84-27 light chain, Envelope glycoprotein E2, ... (4 entities in total) |
| Functional Keywords | fab fragment, immunglobulin fold, antibody, immune system-viral protein complex, immune system/viral protein |
| Biological source | Homo sapiens (human) More |
| Cellular location | Core protein p21: Host endoplasmic reticulum membrane; Single-pass membrane protein (By similarity). Core protein p19: Virion (By similarity). Envelope glycoprotein E1: Virion membrane; Single-pass type I membrane protein (Potential). Envelope glycoprotein E2: Virion membrane; Single-pass type I membrane protein (Potential). p7: Host endoplasmic reticulum membrane; Multi-pass membrane protein. Protease NS2-3: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). Non-structural protein 4A: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential). Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein. Non-structural protein 5A: Host endoplasmic reticulum membrane; Peripheral membrane protein. RNA-directed RNA polymerase: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential): P27958 |
| Total number of polymer chains | 12 |
| Total formula weight | 209724.16 |
| Authors | |
| Primary citation | Krey, T.,Meola, A.,Keck, Z.Y.,Damier-Piolle, L.,Foung, S.K.,Rey, F.A. Structural basis of HCV neutralization by human monoclonal antibodies resistant to viral neutralization escape. Plos Pathog., 9:e1003364-e1003364, 2013 Cited by PubMed Abstract: The high mutation rate of hepatitis C virus allows it to rapidly evade the humoral immune response. However, certain epitopes in the envelope glycoproteins cannot vary without compromising virus viability. Antibodies targeting these epitopes are resistant to viral escape from neutralization and understanding their binding-mode is important for vaccine design. Human monoclonal antibodies HC84-1 and HC84-27 target conformational epitopes overlapping the CD81 receptor-binding site, formed by segments aa434-446 and aa610-619 within the major HCV glycoprotein E2. No neutralization escape was yet observed for these antibodies. We report here the crystal structures of their Fab fragments in complex with a synthetic peptide comprising aa434-446. The structures show that the peptide adopts an α-helical conformation with the main contact residues F⁴⁴² and Y⁴⁴³ forming a hydrophobic protrusion. The peptide retained its conformation in both complexes, independently of crystal packing, indicating that it reflects a surface feature of the folded glycoprotein that is exposed similarly on the virion. The same residues of E2 are also involved in interaction with CD81, suggesting that the cellular receptor binds the same surface feature and potential escape mutants critically compromise receptor binding. In summary, our results identify a critical structural motif at the E2 surface, which is essential for virus propagation and therefore represents an ideal candidate for structure-based immunogen design for vaccine development. PubMed: 23696737DOI: 10.1371/journal.ppat.1003364 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.22 Å) |
Structure validation
Download full validation report
