Backbone NMR resonance assignments for the VP1u N-terminal receptor-binding domain of the human parvovirus pathogen B19

TL;DR

This study provides the first NMR resonance assignments for the receptor-binding domain of the human parvovirus B19, offering a foundation for future drug development.

Contribution

The paper presents the first experimental NMR backbone assignments for the B19V VP1u receptor-binding domain.

Findings

The RBD of B19V forms a stable structure with three helices connected by tight turns.

NMR chemical shifts align well with AlphaFold's predicted structure, confirming its accuracy.

The RBD construct is suitable for future NMR studies and antiviral drug development.

Abstract

Parvovirus B19 (B19V) is a human pathogen that is the causative agent of several diseases in infants and adults. Due to a lack of antivirals against this virus, treatment options are limited. The minor capsid protein of B19V has a unique N terminus, named VP1u, which is essential for infection. The VP1u encodes a receptor binding domain (RBD), necessary for host cell entry, and a phospholipase A2 (PLA2) domain, crucial for endosomal escape during cellular trafficking. Both domains are indispensable for infection, making the RBD a plausible drug target for inhibitors against B19V, as it is located on the exterior surface of the virus. To date, no experimental structural information has been available for the VP1u component for any Parvovirus. Here we report the backbone NMR resonance assignments for the RBD of B19V and demonstrate it forms a stable structure. The backbone chemical shifts are in good agreement with a structure predicted by AlphaFold, validating that the RBD contains three helices connected by tight turns. This RBD construct can now be used for further NMR studies, including assignment of full-length VP1u, determination of protein-protein interaction interfaces, and development of B19 antivirals specific to the RBD domain.

Database: BMRB submission code: 52440

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