ISDA: 9MNS

Deposition Date 2024-12-23

Release Date 2026-01-14

Last Version Date 2026-08-26

Entry Detail

PDB ID:

9MNS

Keywords:

VIRAL PROTEIN/IMMUNE SYSTEM

Title:

Structure of Hepatitis C virus envelope glycoprotein E2 core from genotype 6a bound to broadly neutralizing antibody RM1-36

Biological Source:

Source Organism(s):

Macaca mulatta (Taxon ID: 9544)
Recombinant Hepatitis C virus HK6a/JFH-1 (Taxon ID: 595609)

Expression System(s):

Homo sapiens

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

2.89 Å

R-Value Free:

0.24

R-Value Work:

0.23

R-Value Observed:

0.23

Space Group:

P 1 21 1

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Macromolecular Entities

Structures with similar UniProt ID

Structural Superimposition Protein Blast

Polymer Type:polypeptide(L)
Molecule:Envelope glycoprotein E2
Chain IDs:E, F (auth: B)
Chain Length:231
Number of Molecules:2
Biological Source:Recombinant Hepatitis C virus HK6a/JFH-1

UniProt ID:B9V0E2

Polymer Type:polypeptide(L)
Molecule:RM1-36 Fab heavy chain
Chain IDs:A (auth: H), D (auth: h)
Chain Length:222
Number of Molecules:2
Biological Source:Macaca mulatta

Polymer Type:polypeptide(L)
Molecule:RM1-36 Fab light chain
Chain IDs:B (auth: L), C (auth: l)
Chain Length:211
Number of Molecules:2
Biological Source:Macaca mulatta

Ligand Molecules

NAG

Primary Citation

Structural and genetic signatures of two classes of HCV E2 neutralizing face antibodies from non-human primates immunized with a recombinant E1E2.

Nguyen, Y.T.K, Chen, F, Giang, E, Saha, S, Ueno, L.A, Chen, C, Watson, C.T, Tzarum, N, Wilson, I.A, Law, M, Stanfield, R.L.Show

Npj Vaccines 11 ? ? (2026)

PMID: 42009696 DOI: 10.1038/s41541-026-01449-1

Abstact

Hepatitis C continues to be a significant public health problem despite advancements in antiviral therapeutics. To eliminate this disease, an effective vaccine against new infections and re-infections is needed. However, to date only one Hepatitis C virus (HCV) envelope protein (E1E2) immunogen, developed by Chiron Inc., has been tested in a Phase I clinical trial (ClinicalTrials.gov identifier NCT00500747). To establish a benchmark for elicitation of broadly neutralizing antibodies (bnAbs) by E1E2, we previously immunized non-human primates (NHPs) with this immunogen and isolated monoclonal nAbs that exhibit neutralization potency comparable to human nAbs. Here we show that NHP nAbs, encoded by germline genes IGHV1-138*01 and IGHV4-NL_5*01 (homologs of human IGHV1-69*10 and IGHV4-59*12, respectively), recognize a relatively conserved E2 region (neutralizing face) proximal to antigenic region 3 (AR3). These NHP AR3-targeting nAbs share highly similar binding modes to human AR3-targeting nAbs, suggesting a similarity in human and NHP immune responses to the same HCV immunogen.

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Disease

Primary Citation of related structures

Abstact

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