The structure of helical lipoprotein lipase reveals an unexpected twist in lipase storage.
cryo-electron microscopy
helical reconstruction
lipoprotein lipase
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
12 05 2020
12 05 2020
Historique:
pubmed:
26
4
2020
medline:
31
7
2020
entrez:
26
4
2020
Statut:
ppublish
Résumé
Lipases are enzymes necessary for the proper distribution and utilization of lipids in the human body. Lipoprotein lipase (LPL) is active in capillaries, where it plays a crucial role in preventing dyslipidemia by hydrolyzing triglycerides from packaged lipoproteins. Thirty years ago, the existence of a condensed and inactive LPL oligomer was proposed. Although recent work has shed light on the structure of the LPL monomer, the inactive oligomer remained opaque. Here we present a cryo-EM reconstruction of a helical LPL oligomer at 3.8-Å resolution. Helix formation is concentration-dependent, and helices are composed of inactive dihedral LPL dimers. Heparin binding stabilizes LPL helices, and the presence of substrate triggers helix disassembly. Superresolution fluorescent microscopy of endogenous LPL revealed that LPL adopts a filament-like distribution in vesicles. Mutation of one of the helical LPL interaction interfaces causes loss of the filament-like distribution. Taken together, this suggests that LPL is condensed into its inactive helical form for storage in intracellular vesicles.
Identifiants
pubmed: 32332168
pii: 1916555117
doi: 10.1073/pnas.1916555117
pmc: PMC7229681
doi:
Substances chimiques
Triglycerides
0
Lipoprotein Lipase
EC 3.1.1.34
Banques de données
PDB
['6U7M']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10254-10264Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL125654
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM122510
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIC ES103326
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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