Proteomics

Dataset Information

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Structural, biochemical and functional characterization of the essential host factor SETD3 in complex with the enterovirus CV-B3 2A protease


ABSTRACT: Enteroviruses cause a number of medically relevant and widespread human diseases with no approved antiviral therapies currently available. We have previously identified the actin histidine methyltransferase SETD3 as critically important for enterovirus infection through a protein-protein interaction with the viral protease 2A. Here, we report the cryo-EM structure of SETD3 in complex with coxsackievirus B3 2A at 3.5 Å resolution. 2A interacts with two distinct interfaces on SETD3, one in the SET domain that overlaps with the actin binding interface, and one in the RSB domain. Structure-function analysis revealed that mutations of key residues in the SET interaction interface resulted in severely reduced binding to 2A and a complete protection from enteroviral infection. Altogether, our findings provide key structural insights into the interaction between SETD3 and 2A and provide a framework for the rational design of host targeted therapeutics against this class of viruses.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hek-293t Cell, Kidney Epithelial Cell

SUBMITTER: Ruth Huttenhain  

LAB HEAD: Nevan Krogan

PROVIDER: PXD024127 | Pride | 2022-10-14

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
Experimental_design_SET3_mutants_Flag.txt Txt
Experimental_design_SETD3_2A_purification.txt Txt
Experimental_design_SETD3_flag.txt Txt
SETD3_IP_evidence.txt Txt
SETD3_IP_peptides.txt Txt
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Publications


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, inclu  ...[more]

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