Purification and structure of luminal domain C of human Niemann-Pick C1 protein

Acta Crystallogr F Struct Biol Commun. 2023 Feb 1;79(Pt 2):45-50. doi: 10.1107/S2053230X23000705. Epub 2023 Feb 2.

Abstract

Niemann-Pick C1 protein (NPC1) is a membrane protein that primarily resides in late endosomes and lysosomes, and plays an important role in cholesterol homeostasis in the cell. The second luminal domain of NPC1 (NPC1-C) serves as the intracellular receptor for Ebola and Marburg viruses. Here, the recombinant production of nonglycosylated and glycosylated NPC1-C and a new crystal form of the nonglycosylated protein are reported. The crystals belonged to space group P21 and diffracted to 2.3 Å resolution. The structure is similar to other reported structures of NPC1-C, with differences observed in the protruding loops when compared with NPC1-C in complex with Ebola virus glycoprotein or NPC2.

Keywords: Ebola virus; Niemann–Pick C1 protein; cholesterol; membrane proteins.

MeSH terms

  • Crystallography, X-Ray
  • Glycoproteins / chemistry
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lysosomes / metabolism
  • Membrane Glycoproteins* / chemistry
  • Membrane Glycoproteins* / genetics
  • Membrane Glycoproteins* / metabolism
  • Niemann-Pick C1 Protein* / metabolism

Substances

  • Membrane Glycoproteins
  • Niemann-Pick C1 Protein
  • Intracellular Signaling Peptides and Proteins
  • Glycoproteins