About: Inter-domain dynamics drive cholesterol transport by NPC1 and NPC1L1 proteins

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: Inter-domain dynamics drive cholesterol transport by NPC1 and NPC1L1 proteins Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Inter-domain dynamics drive cholesterol transport by NPC1 and NPC1L1 proteins
Creator	Pfeffer, Suzanne Caldwell, Jenna Elghobashi-Meinhardt, Nadia Elias, Joshua Lu, Albert »more»
topic	covid:29a113c5a7a094168d2ced177ac811366a14052a#this
source	PMC
abstract	Transport of LDL-derived cholesterol from lysosomes into the cytoplasm requires NPC1 protein; NPC1L1 mediates uptake of dietary cholesterol. We introduced single disulfide bonds into NPC1 and NPC1L1 to explore the importance of inter-domain dynamics in cholesterol transport. Using a sensitive method to monitor lysosomal cholesterol efflux, we found that NPC1’s N-terminal domain need not release from the rest of the protein for efficient cholesterol export. Either introducing single disulfide bonds to constrain lumenal/extracellular domains or shortening a cytoplasmic loop abolishes transport activity by both NPC1 and NPC1L1. The widely prescribed cholesterol uptake inhibitor, ezetimibe, blocks NPC1L1; we show that residues that lie at the interface between NPC1L1's three extracellular domains comprise the drug’s binding site. These data support a model in which cholesterol passes through the cores of NPC1/NPC1L1 proteins; concerted movement of various domains is needed for transfer and ezetimibe blocks transport by binding to multiple domains simultaneously.
has issue date	2020-05-15(xsd:dateTime)
bibo:doi	10.7554/elife.57089
bibo:pmid	32410728
has license	cc-by
sha1sum (hex)	29a113c5a7a094168d2ced177ac811366a14052a
schema:url	https://doi.org/10.7554/elife.57089
resource representing a document's title	Inter-domain dynamics drive cholesterol transport by NPC1 and NPC1L1 proteins
has PubMed Central identifier	PMC7228765
has PubMed identifier	32410728
resource representing a document's body	covid:29a113c5a7a094168d2ced177ac811366a14052a#body_text
is http://vocab.deri.ie/void#inDataset of	proxy:http/ns.inria.fr/covid19/29a113c5a7a094168d2ced177ac811366a14052a
is schema:about of	named entity 'NPC1' named entity 'ezetimibe' named entity 'domains' named entity 'cholesterol' named entity 'protein' »more»

Faceted Search & Find service v1.13.91 as of Mar 24 2020

Alternative Linked Data Documents: Sponger | ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2025 OpenLink Software