Lysosomal cholesterol export reconstituted from fragments of Niemann-Pick C1

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Niemann-Pick C1 (NPC1) is a polytopic membrane protein with 13 transmembrane helices that exports LDL-derived cholesterol from lysosomes by carrying it through the 80 Å glycocalyx and the 40 Å lipid bilayer. Transport begins when cholesterol binds to the N-terminal domain (NTD) of NPC1, which projects to the surface of the glycocalyx. Here, we reconstitute cholesterol transport by expressing the NTD as a fragment separate from the remaining portion of NPC1. When co-expressed, the two NPC1 fragments reconstitute cholesterol transport, indicating that the NTD has the flexibility to interact with the remaining parts of NPC1 even when not covalently linked. We also show that cholesterol can be transferred from the NTD of one full-length NPC1 to another NPC1 molecule that lacks the NTD. These data support the hypothesis that cholesterol is transported through interactions between two or more NPC1 molecules.

Original languageEnglish (US)
Article numbere38564
JournaleLife
Volume7
DOIs
StatePublished - Jul 26 2018

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Cholesterol
Glycocalyx
Lipid Bilayers
Lysosomes
Molecules
Lipid bilayers
LDL Cholesterol
Membrane Proteins

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Lysosomal cholesterol export reconstituted from fragments of Niemann-Pick C1. / Trinh, Michael Nguyen; Brown, Michael S.; Seemann, Joachim; Goldstein, Joseph L.; Lu, Feiran.

In: eLife, Vol. 7, e38564, 26.07.2018.

Research output: Contribution to journalArticle

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AU - Brown, Michael S.

AU - Seemann, Joachim

AU - Goldstein, Joseph L.

AU - Lu, Feiran

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