7LMS

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

Summary for 7LMS

• Entry DOI: 10.2210/pdb7lms/pdb
• EMDB information: 23441
• Descriptor: Protease 2A, Actin-histidine N-methyltransferase, ZINC ION, ... (4 entities in total)
• Functional Keywords: methyltransferase, viral protease, viral protein
• Biological source: Coxsackievirus B3 (strain Nancy); More
• Total number of polymer chains: 2
• Total formula weight: 84517.42

Authors

Verba, K.A.,Schulze-Gahmen, U. (deposition date: 2021-02-05, release date: 2022-08-10, Last modification date: 2024-05-29)

Primary citation

Peters, C.E.,Schulze-Gahmen, U.,Eckhardt, M.,Jang, G.M.,Xu, J.,Pulido, E.H.,Bardine, C.,Craik, C.S.,Ott, M.,Gozani, O.,Verba, K.A.,Huttenhain, R.,Carette, J.E.,Krogan, N.J.
Structure-function analysis of enterovirus protease 2A in complex with its essential host factor SETD3.
Nat Commun, 13:5282-5282, 2022

PubMed 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.

PubMed: 36075902
DOI: 10.1038/s41467-022-32758-3

Experimental method

ELECTRON MICROSCOPY (3.5 Å)