Palmitoylated acyl protein thioesterase APT2 deforms membranes to extract substrate acyl chains.
Journal
Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
09
06
2020
accepted:
26
01
2021
revised:
27
12
2020
pubmed:
13
3
2021
medline:
29
4
2021
entrez:
12
3
2021
Statut:
ppublish
Résumé
Many biochemical reactions require controlled recruitment of proteins to membranes. This is largely regulated by posttranslational modifications. A frequent one is S-acylation, which consists of the addition of acyl chains and can be reversed by poorly understood acyl protein thioesterases (APTs). Using a panel of computational and experimental approaches, we dissect the mode of action of the major cellular thioesterase APT2 (LYPLA2). We show that soluble APT2 is vulnerable to proteasomal degradation, from which membrane binding protects it. Interaction with membranes requires three consecutive steps: electrostatic attraction, insertion of a hydrophobic loop and S-acylation by the palmitoyltransferases ZDHHC3 or ZDHHC7. Once bound, APT2 is predicted to deform the lipid bilayer to extract the acyl chain bound to its substrate and capture it in a hydrophobic pocket to allow hydrolysis. This molecular understanding of APT2 paves the way to understand the dynamics of APT2-mediated deacylation of substrates throughout the endomembrane system.
Identifiants
pubmed: 33707782
doi: 10.1038/s41589-021-00753-2
pii: 10.1038/s41589-021-00753-2
pmc: PMC7610442
mid: EMS114923
doi:
Substances chimiques
Proteins
0
LYPLA2 protein, human
EC 3.1.2.-
Thiolester Hydrolases
EC 3.1.2.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
438-447Subventions
Organisme : Swiss National Science Foundation
ID : 176393
Pays : Switzerland
Organisme : Swiss National Science Foundation
ID : 192608
Pays : Switzerland
Organisme : European Research Council
ID : 340260
Pays : International
Commentaires et corrections
Type : CommentIn
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