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

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Direct Mechanisms in Cholesterol Modulation of Protein Function

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1135))

Abstract

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.

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Abbreviations

CLR:

Cholesterol

CTD:

C-terminal domain

MLD:

Middle luminal domain

NPC:

Niemann-Pick Type C

NTD:

N-terminal domain

SSD:

Sterol sensing domain

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Authors and Affiliations

  1. Department of Chemistry, University of Illinois at Chicago, Chicago, IL, USA

    Stephanie M. Cologna & Avia Rosenhouse-Dantsker

  2. Laboratory for Integrative Neuroscience, University of Illinois at Chicago, Chicago, IL, USA

    Stephanie M. Cologna

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Correspondence to Stephanie M. Cologna or Avia Rosenhouse-Dantsker .

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Editors and Affiliations

  1. Department of Chemistry, University of Illinois, Chicago, IL, USA

    Avia Rosenhouse-Dantsker

  2. Department of Pharmacology, The University of Tennessee HSC, Memphis, TN, USA

    Anna N. Bukiya

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Cologna, S.M., Rosenhouse-Dantsker, A. (2019). Insights into the Molecular Mechanisms of Cholesterol Binding to the NPC1 and NPC2 Proteins. In: Rosenhouse-Dantsker, A., Bukiya, A. (eds) Direct Mechanisms in Cholesterol Modulation of Protein Function. Advances in Experimental Medicine and Biology, vol 1135. Springer, Cham. https://doi.org/10.1007/978-3-030-14265-0_8

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