EMD-31567

Single-particle
3.0 Å
EMD-31567 Deposition: 23/07/2021
Map released: 20/10/2021
Last modified: 20/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-31567

Structure of Venezuelan equine encephalitis virus with the receptor LDLRAD3

EMD-31567

Single-particle
3.0 Å
EMD-31567 Deposition: 23/07/2021
Map released: 20/10/2021
Last modified: 20/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Venezuelan equine encephalitis virus (strain TC-83), Homo sapiens
Sample: Venezuelan equine encephalitis virus (strain TC-83)
Fitted models: 7fff (Avg. Q-score: 0.48)

Deposition Authors: Zhang X , Xiang Y
Structure of Venezuelan equine encephalitis virus with its receptor LDLRAD3.
Ma B, Huang C, Ma J, Xiang Y , Zhang X
(2021) Nature , 598 , 677 - 681
PUBMED: 34646021
DOI: doi:10.1038/s41586-021-03909-1
ISSN: 1476-4687
ASTM: NATUAS
Abstract:
Venezuelan equine encephalitis virus (VEEV) is an enveloped RNA virus that causes encephalitis and potentially mortality in infected humans and equines1. At present, no vaccines or drugs are available that prevent or cure diseases caused by VEEV. Low-density lipoprotein receptor class A domain-containing 3 (LDLRAD3) was recently identified as a receptor for the entry of VEEV into host cells2. Here we present the cryo-electron microscopy structure of the LDLRAD3 extracellular domain 1 (LDLRAD3-D1) in complex with VEEV virus-like particles at a resolution of 3.0 Å. LDLRAD3-D1 has a cork-like structure and is inserted into clefts formed between adjacent VEEV E2-E1 heterodimers in the viral-surface trimer spikes through hydrophobic and polar contacts. Mutagenesis studies of LDLRAD3-D1 identified residues that are involved in the key interactions with VEEV. Of note, some of the LDLRAD3-D1 mutants showed a significantly increased binding affinity for VEEV, suggesting that LDLRAD3-D1 may serve as a potential scaffold for the development of inhibitors of VEEV entry. Our structures provide insights into alphavirus assembly and the binding of receptors to alphaviruses, which may guide the development of therapeutic countermeasures against alphaviruses.