PMID: 27238017

 

    Legend: Gene, Sites

Title : Structural Insights into the Niemann-Pick C1 ( NPC1 )-Mediated Cholesterol Transfer and Ebola Infection

Abstract :

1. Niemann-Pick disease type C (NPC ) is associated with mutations in NPC1 and NPC2 , whose gene products are key players in the endosomal/lysosomal egress of low-density lipoprotein-derived cholesterol
2. NPC1 is also the intracellular receptor for Ebola virus (EBOV)
3. Here, we present a 4.4 Å structure of full-length human NPC1 and a low-resolution reconstruction of NPC1 in complex with the cleaved glycoprotein ( GPcl ) of EBOV, both determined by single-particle electron cryomicroscopy
4. NPC1 contains 13 transmembrane segments (TMs) and three distinct lumenal domains A (also designated NTD ), C, and I. TMs 2-13 exhibit a typical resistance-nodulation-cell division fold, among which TMs 3-7 constitute the sterol-sensing domain conserved in several proteins involved in cholesterol metabolism and signaling
5. A trimeric EBOV- GPcl binds to one NPC1 monomer through the domain C
6. Our structural and biochemical characterizations provide an important framework for mechanistic understanding of NPC1-mediated intracellular cholesterol trafficking and Ebola virus infection

Output (sent_index, trigger, protein, sugar, site):

• 3. glycoprotein, , GPcl, -, -
• 3. glycoprotein, , glycoprotein, -, -

Output(Part-Of) (sent_index, protein, site):

• 4. NPC1, domains

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX
NPC2	10577	1
NPC1	4864	0,1,2,3,4,5,6
TMs 3-7	7170	4
C (NPC	4864	1
NTD	80199	4