PXD054077

PXD054077 is an original dataset announced via ProteomeXchange.

Title	Targeting APT2 improves MAVS palmitoylation and antiviral innate immunity
Description	Innate immunity serves as the primary defense against viral and microbial infections in humans. Among its components, retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are well-characterized intracellular pattern-recognition proteins that trigger innate immune responses upon viral infection. However, the precise influence of cellular metabolites, especially fatty acids, on the regulation of RLR-mediated antiviral innate immunity remains largely elusive. Here, through screening a metabolite library, palmitic acid (PA) has been identified as a crucial metabolite responsible for modulating antiviral infections. Mechanistically, PA induces the palmitoylation of MAVS, leading to MAVS aggregation and subsequent activation, thereby enhancing the innate immune response against viral infections. Functionally, the enzyme palmitoyl-transferase ZDHHC24 plays a key role in catalyzing the palmitoylation of MAVS at both C46 and C79 residues, thereby facilitating the transduction of RLR-mediated TBK1-IRF3-IFN signaling pathway, particularly under conditions of PA stimulation or high-fat diet feeding. Conversely, the absence of ZDHHC24 significantly attenuates virus-induced innate immune responses in both cells and mice. Moreover, APT2 counteracts with ZDHHC24 to de-palmitoylate MAVS, thus inhibiting the antiviral response. Consequently, inhibition of APT2 using compounds like ML349 effectively reverses MAVS palmitoylation and activation in response to antiviral infections. These findings underscore the critical role of PA and ZDHHC24 in regulating antiviral innate immunity through MAVS palmitoylation, and suggest potential therapeutic strategies for combating viral infections, such as enhancing PA intake or specifically targeting APT2.
HostingRepository	PRIDE
AnnounceDate	2024-09-10
AnnouncementXML	Submission_2024-09-09_19:24:56.943.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yi Zhang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	palmitoylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-20 02:40:40	ID requested
⏵ 1	2024-09-09 19:24:57	announced

10.1016/J.MOLCEL.2024.08.014;

submitter keyword: Human，MAVS，LC-MSMS

Bu lang
contact affiliation	sun yat-sen university
contact email	bulang@mail3.sysu.edu.cn
lab head
Yi Zhang
contact affiliation	Sun yat-sen university
contact email	wjzy960217@163.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD054077
     1. Label: PRIDE project
     2. Name: Targeting APT2 improves MAVS palmitoylation and antiviral innate immunity