Comparison of the structure-function properties of wild-type human apoA-V and a C-terminal truncation associated with elevated plasma triglycerides.
APOA5
TRL metabolism
apolipoprotein
triglyceride metabolism
Journal
medRxiv : the preprint server for health sciences
Titre abrégé: medRxiv
Pays: United States
ID NLM: 101767986
Informations de publication
Date de publication:
23 Feb 2023
23 Feb 2023
Historique:
pubmed:
4
3
2023
medline:
4
3
2023
entrez:
3
3
2023
Statut:
epublish
Résumé
Plasma triglycerides (TGs) are causally associated with coronary artery disease and acute pancreatitis. Apolipoprotein A-V (apoA-V, gene We used hydrogen-deuterium exchange mass spectrometry to determine the secondary structure of human apoA-V in lipid-free and lipid-associated conditions and identified a C-terminal hydrophobic face. Then, we used genomic data in the Penn Medicine Biobank to identify a rare variant, Q252X, predicted to specifically eliminate this region. We interrogated the function of apoA-V Q252X using recombinant protein Human apoA-V Q252X carriers exhibited elevated plasma TG levels consistent with loss of function. Deletion of apoA-V's C-terminus leads to reduced apoA-V bioavailability
Sections du résumé
Background
UNASSIGNED
Plasma triglycerides (TGs) are causally associated with coronary artery disease and acute pancreatitis. Apolipoprotein A-V (apoA-V, gene
Methods
UNASSIGNED
We used hydrogen-deuterium exchange mass spectrometry to determine the secondary structure of human apoA-V in lipid-free and lipid-associated conditions and identified a C-terminal hydrophobic face. Then, we used genomic data in the Penn Medicine Biobank to identify a rare variant, Q252X, predicted to specifically eliminate this region. We interrogated the function of apoA-V Q252X using recombinant protein
Results
UNASSIGNED
Human apoA-V Q252X carriers exhibited elevated plasma TG levels consistent with loss of function.
Conclusions
UNASSIGNED
Deletion of apoA-V's C-terminus leads to reduced apoA-V bioavailability
Identifiants
pubmed: 36865344
doi: 10.1101/2023.02.21.23286268
pmc: PMC9980232
pii:
doi:
Types de publication
Preprint
Langues
eng