# X-ray structure of RM1-38 antibody bound to hepatitis C HVR1 peptide shows a flexible viral shield

- Published: 2026-11-11 08:47 UTC
- Section: Life & Health › Medicine
- Tags: hepatitis C virus, hypervariable region 1, E1E2 glycoprotein, RM1-38 antibody, antigenic site 399, SR-BI receptor, CD81, negative-stain electron microscopy, broadly neutralizing antibodies, immune evasion
- URL: https://realtech.media/news/rt-5ad636b1f54e7702e76ae135_x_ray_structure/

**Researchers resolved how antibody RM1-38 recognizes the C-terminal part of HVR1, a region unresolved in all E1E2 structures so far, and tested its effect on neutralization and receptor binding.**

![X-ray structure of RM1-38 antibody bound to hepatitis C HVR1 peptide shows a flexible viral shield](https://realtech.media/media/2026/11/b02e01cfb8d8f330.jpg)
*Jazzlw, Wikimedia Commons, CC BY-SA 4.0*

A structural study of hypervariable region 1 (HVR1) of the hepatitis C virus E1E2 glycoprotein was published in Proceedings of the National Academy of Sciences. HVR1 mutates rapidly and shields conserved neutralizing epitopes, which contributes to immune evasion [1]. In all published E1E2 or E2 structures, the C-terminal part of HVR1 (residues 394 to 411) remains unresolved [1]. The authors used the neutralizing antibody RM1-38, which targets residues 399 to 409, a site they call antigenic site 399 (AS399).

## Structure and flexibility of HVR1

The crystal structure of the RM1-38 Fab with the HVR1 AS399 peptide, combined with mutagenesis analysis, delineated the molecular basis of the antibody's strain-specific recognition and neutralization [1]. Negative-stain electron microscopy (nsEM) and competition enzyme-linked immunosorbent assay showed that HVR1 has pronounced conformational flexibility, even when other neutralizing antibodies are bound to E1E2 [1].

## Effects on neutralization and receptor binding

In virus neutralization assays that combined RM1-38 with broadly neutralizing antibodies, RM1-38 showed antagonistic effects with them [1]. RM1-38 also reduced E1E2 binding to cells expressing the scavenger receptor SR-BI, an HVR1-dependent receptor. It did not affect binding to the CD81 tetraspanin [1].

The authors report that these findings support a model in which HVR1 works as a dynamic shield. In this model, its conformational plasticity contributes both to receptor engagement and to evasion of humoral immunity in persistent infection [1]. The work combines X-ray crystallography, electron microscopy and laboratory binding and neutralization assays.

## Sources

1. [Proceedings of the National Academy of Sciences](https://doi.org/10.1073/pnas.2606727123)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-5ad636b1f54e7702e76ae135_x_ray_structure/