PXD024127

PXD024127 is an original dataset announced via ProteomeXchange.

Title	Structural, biochemical and functional characterization of the essential host factor SETD3 in complex with the enterovirus CV-B3 2A protease
Description	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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:57:37.942.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ruth Huttenhain
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-11 02:25:13	ID requested
1	2022-10-13 19:35:26	announced
⏵ 2	2023-11-14 07:57:38	announced	2023-11-14: Updated project metadata.

Peters CE, Schulze-Gahmen U, Eckhardt M, Jang GM, Xu J, Pulido EH, Bardine C, Craik CS, Ott M, Gozani O, Verba KA, H, ü, ttenhain R, Carette JE, Krogan NJ, Structure-function analysis of enterovirus protease 2A in complex with its essential host factor SETD3. Nat Commun, 13(1):5282(2022) [pubmed]

submitter keyword: AP-MS, host-pathogen interactions, enterovirus,SETD3, 2A protease

Nevan Krogan
contact affiliation	UCSF
contact email	ruth.huttenhain@ucsf.edu
lab head
Ruth Huttenhain
contact affiliation	UCSF
contact email	ruth.huttenhain@ucsf.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/10/PXD024127

PRIDE project URI

• PRIDE
  1. PXD024127
     1. Label: PRIDE project
     2. Name: Structural, biochemical and functional characterization of the essential host factor SETD3 in complex with the enterovirus CV-B3 2A protease