Thinking outside the CaaX-box: an unusual reversible prenylation on ALDH9A1

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F23%3A73619830" target="_blank" >RIV/61989592:15310/23:73619830 - isvavai.cz</a>

Result on the web

<a href="https://pubs.rsc.org/en/content/articlelanding/2023/cb/d3cb00089c" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2023/cb/d3cb00089c</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/D3CB00089C" target="_blank" >10.1039/D3CB00089C</a>

Result language

angličtina

Original language name

Thinking outside the CaaX-box: an unusual reversible prenylation on ALDH9A1

Original language 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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10406 - Analytical chemistry

Project

<a href="/en/project/8J23FR011" target="_blank" >8J23FR011: Engineering of methionine and aldehyde metabolizing enzymes linked to human diseases including cancer</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

RSC CHEMICAL BIOLOGY

ISSN

2633-0679

e-ISSN

2633-0679

Volume of the periodical

4

Issue of the periodical within the volume

11

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

913-925

UT code for WoS article

001089185800001

EID of the result in the Scopus database

2-s2.0-85170534410