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Title | Structure-function analysis of enterovirus protease 2A in complex with its essential host factor SETD3. |
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Journal, issue, pages | Nat Commun, Vol. 13, Issue 1, Page 5282, Year 2022 |
Publish date | Sep 8, 2022 |
Authors | Christine E Peters / Ursula Schulze-Gahmen / Manon Eckhardt / Gwendolyn M Jang / Jiewei Xu / Ernst H Pulido / Conner Bardine / Charles S Craik / Melanie Ott / Or Gozani / Kliment A Verba / Ruth Hüttenhain / Jan E Carette / Nevan J Krogan / |
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 ...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. |
External links | Nat Commun / PubMed:36075902 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.5 Å |
Structure data | EMDB-23441, PDB-7lms: |
Chemicals | ChemComp-ZN: ChemComp-SAH: |
Source |
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Keywords | VIRAL PROTEIN / Methyltransferase / viral protease |