+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Insights into the Molecular Mechanisms of Cholesterol Binding to the NPC1 and NPC2 Proteins



Insights into the Molecular Mechanisms of Cholesterol Binding to the NPC1 and NPC2 Proteins



Advances in Experimental Medicine and Biology 1135: 139-160



In recent years, a growing number of studies have implicated the coordinated action of NPC1 and NPC2 in intralysosomal transport and efflux of cholesterol. Our current understanding of this process developed with just over two decades of research. Since the cloning of the genes encoding the NPC1 and NPC2 proteins, studies of the biochemical defects observed when either gene is mutated along with computational and structural studies have unraveled key steps in the underlying mechanism. Here, we summarize the major contributions to our understanding of the proposed cholesterol transport controlled by NPC1 and NPC2, and briefly discuss recent findings of cholesterol binding and transport proteins beyond NPC1 and NPC2. We conclude with key questions and major challenges for future research on cholesterol transport by the NPC1 and NPC2 proteins.

(PDF emailed within 0-6 h: $19.90)

Accession: 066792739

Download citation: RISBibTeXText

PMID: 31098815

DOI: 10.1007/978-3-030-14265-0_8


Related references

Ultrastructural Similarity of Storage Bodies in Neurons Lacking NPC1, NPC2, or Both Proteins Suggest NPC1-NPC2 Molecular Co-operativity in Lipid Trafficking. Microscopy and Microanalysis 10(S02): 1468-1469, 2004

Glycosphingolipid - cholesterol abnormalities in NPC2 - deficient neurons appear equivalent to those occurring in neurons lacking NPC1, suggesting NPC1 - NPC2 molecular cooperation. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 537 15, 2003

Computational studies of the cholesterol transport between NPC2 and the N-terminal domain of NPC1 (NPC1(NTD)). Biochemistry 52(39): 6879-6891, 2014

Niemann-Pick type C disease: a QM/MM study of conformational changes in cholesterol in the NPC1(NTD) and NPC2 binding pockets. Biochemistry 53(41): 6603-6614, 2015

NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes. Proceedings of the National Academy of Sciences of the United States of America 105(40): 15287-15292, 2008

NPC1 and NPC2 regulate cellular cholesterol homeostasis through generation of low density lipoprotein cholesterol-derived oxysterols. Journal of Biological Chemistry 278(28): 25517-25525, 2003

NPC1/NPC2 function as a tag team duo to mobilize cholesterol. Proceedings of the National Academy of Sciences of the United States of America 105(40): 15223-4, 2008

A role for NPC1 and NPC2 in intestinal cholesterol absorption--the hypothesis gutted. Biochemical Journal 408(1): E1-E3, 2007

Do mammalian NPC1 and NPC2 play a role in intestinal cholesterol absorption?. Biochemical Journal 408(1): 1-5, 2007

Simulations of NPC1(NTD):NPC2 Protein Complex Reveal Cholesterol Transfer Pathways. International Journal of Molecular Sciences 19(9), 2018

Transport Assays for Sterol-Binding Proteins: Stopped-Flow Fluorescence Methods for Investigating Intracellular Cholesterol Transport Mechanisms of NPC2 Protein. Methods in Molecular Biology 1583: 97-110, 2018

Structure of glycosylated NPC1 luminal domain C reveals insights into NPC2 and Ebola virus interactions. Febs Letters 590(5): 605-612, 2016

Physiological and coordinate downregulation of the NPC1 and NPC2 genes are associated with the sequestration of LDL-derived cholesterol within endocytic compartments. Journal of Cellular Biochemistry 108(5): 1102-1116, 2010

Clues to the mechanism of cholesterol transfer from the structure of NPC1 middle lumenal domain bound to NPC2. Proceedings of the National Academy of Sciences of the United States of America 113(36): 10079-10084, 2018

Quantitative role of LAL, NPC2, and NPC1 in lysosomal cholesterol processing defined by genetic and pharmacological manipulations. Journal of Lipid Research 52(4): 688-698, 2011