EMD-23441

Single-particle
3.5 Å
EMD-23441 Deposition: 05/02/2021
Map released: 10/08/2022
Last modified: 29/05/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-23441

Structure of human SetD3 methyl-transferase in complex with 2A protease from Coxsackievirus B3

EMD-23441

Single-particle
3.5 Å
EMD-23441 Deposition: 05/02/2021
Map released: 10/08/2022
Last modified: 29/05/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Coxsackievirus B3 (strain Nancy), Coxsackievirus B3 (strain Nancy), Homo sapiens
Sample: Ternary complex of Coxsackievirus B3 2A protease and human SetD3 methyltransferase
Fitted models: 7lms (Avg. Q-score: 0.452)

Deposition Authors: Verba KA , Schulze-Gahmen U
Structure-function analysis of enterovirus protease 2A in complex with its essential host factor SETD3.
PUBMED: 36075902
DOI: doi:10.1038/s41467-022-32758-3
ISSN: 2041-1723
Abstract:
Enteroviruses cause a number of medically relevant and widespread human diseases with no approved antiviral therapies currently available. Host-directed therapies present an enticing option for this diverse genus of viruses. We have previously identified the actin histidine methyltransferase SETD3 as a critical host factor physically interacting with the viral protease 2A. Here, we report the 3.5 Å cryo-EM structure of SETD3 interacting with coxsackievirus B3 2A at two distinct interfaces, including the substrate-binding surface within the SET domain. Structure-function analysis revealed that mutations of key residues in the SET domain resulted in severely reduced binding to 2A and complete protection from enteroviral infection. Our findings provide insight into the molecular basis of the SETD3-2A interaction and a framework for the rational design of host-directed therapeutics against enteroviruses.