7FFF

Structure of Venezuelan equine encephalitis virus with the receptor LDLRAD3

This is a non-PDB format compatible entry.

Summary for 7FFF

• Entry DOI: 10.2210/pdb7fff/pdb
• EMDB information: 31567
• Descriptor: Capsid protein, Spike glycoprotein E1, Low-density lipoprotein receptor class A domain-containing protein 3, ... (6 entities in total)
• Functional Keywords: virus, receptor, complex, virus like particle, virus like particle-protein binding complex, virus like particle/protein binding
• Biological source: Venezuelan equine encephalitis virus (strain TC-83) (VEEV); More
• Total number of polymer chains: 20
• Total formula weight: 560760.12

Authors

Zhang, X.,Xiang, Y.,Ma, J.,Ma, B.,Huang, C. (deposition date: 2021-07-23, release date: 2021-10-20, Last modification date: 2021-11-17)

Primary citation

Ma, B.,Huang, C.,Ma, J.,Xiang, Y.,Zhang, X.
Structure of Venezuelan equine encephalitis virus with its receptor LDLRAD3.
Nature, 598:677-681, 2021

PubMed Abstract: Venezuelan equine encephalitis virus (VEEV) is an enveloped RNA virus that causes encephalitis and potentially mortality in infected humans and equines. 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 cells. 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.

PubMed: 34646021
DOI: 10.1038/s41586-021-03909-1

Experimental method

ELECTRON MICROSCOPY (3 Å)