PXD036365-4

PXD036365 is an original dataset announced via ProteomeXchange.

Title	Thinking outside the CaaX-box: an unusual reversible prenylation on ALDH9A1
Description	Protein lipidation is a post-translational modification that confers hydrophobicity on protein substrates to control their cellular localization, mediate protein trafficking, and regulate protein function. In particular, protein prenylation is a C-terminal modification on proteins bearing canonical motifs catalyzed by prenyltransferases. Prenylated proteins have been of interest due to their numerous associations with various diseases. Chemical proteomic approaches have been pursued over the last decade to define prenylated proteomes (prenylome) and probe their responses to perturbations in various cellular systems. Here, we describe the discovery of prenylation of a non-canonical prenylated protein, ALDH9A1, which lacks any apparent prenylation motif. This enzyme was initially identified through chemical proteomic profiling of prenylomes in various cell lines. Metabolic labeling with an isoprenoid probe using overexpressed ALDH9A1 revealed that this enzyme can be prenylated inside cells but does not respond to inhibition by prenyltransferase inhibitors. Site-directed mutagenesis of the key residues involved in ALDH9A1 activity indicates that the catalytic C288 bears the isoprenoid modification likely through an NAD+-dependent mechanism. Furthermore, the isoprenoid modification is also susceptible to hydrolysis, indicating a reversible modification. We hypothesize that this modification originates from endogenous farnesal or geranygeranial, the established degradation products of prenylated proteins and results in a thioester form that accumulates. This novel reversible prenoyl modification on ALDH9A1 expands the current paradigm of protein prenylation by illustrating a potentially new type of protein–lipid modification that may also serve as a novel mechanism for controlling enzyme function
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:13:40.904.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shelby Auger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	farnesylated residue; TMT6plex-126 reporter+balance reagent acylated residue; biotinylated residue; geranylgeranylated residue
Instrument	Orbitrap Fusion Lumos; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-28 03:24:56	ID requested
1	2023-11-06 03:28:59	announced
2	2023-11-14 08:25:09	announced	2023-11-14: Updated project metadata.
3	2023-11-14 08:35:21	announced	2023-11-14: Updated project metadata.
⏵ 4	2024-10-22 06:13:44	announced	2024-10-22: Updated project metadata.

10.1038/s41598-021-83666-3;

10.1039/D3CB00089C;

Suazo KF, Jeong A, Ahmadi M, Brown C, Qu W, Li L, Distefano MD, Metabolic labeling with an alkyne probe reveals similarities and differences in the prenylomes of several brain-derived cell lines and primary cells. Sci Rep, 11(1):4367(2021) [pubmed]

submitter keyword: Prenyaltion, lipidation, ALDH9A1, Prenylomics,Proteomics

Mark D
contact affiliation	Chemistry Department, University of Minnesota, United States
contact email	diste001@umn.edu
lab head
Shelby Auger
contact affiliation	University of Minnesota
contact email	auger054@umn.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036365
     1. Label: PRIDE project
     2. Name: Thinking outside the CaaX-box: an unusual reversible prenylation on ALDH9A1