+Search query
-Structure paper
Title | Structural Insights into the Niemann-Pick C1 (NPC1)-Mediated Cholesterol Transfer and Ebola Infection. |
---|---|
Journal, issue, pages | Cell, Vol. 165, Issue 6, Page 1467-1478, Year 2016 |
Publish date | Jun 2, 2016 |
Authors | Xin Gong / Hongwu Qian / Xinhui Zhou / Jianping Wu / Tao Wan / Pingping Cao / Weiyun Huang / Xin Zhao / Xudong Wang / Peiyi Wang / Yi Shi / George F Gao / Qiang Zhou / Nieng Yan / |
PubMed Abstract | 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. ...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. NPC1 is also the intracellular receptor for Ebola virus (EBOV). 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. 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. A trimeric EBOV-GPcl binds to one NPC1 monomer through the domain C. Our structural and biochemical characterizations provide an important framework for mechanistic understanding of NPC1-mediated intracellular cholesterol trafficking and Ebola virus infection. |
External links | Cell / PubMed:27238017 / PubMed Central |
Methods | EM (single particle) |
Resolution | 4.43 - 6.7 Å |
Structure data | EMDB-6640: cryo-EM map of the full-length human NPC1 at 4.4 angstrom EMDB-6641: |
Chemicals | ChemComp-NAG: ChemComp-CLR: |
Source |
|
Keywords | MEMBRANE PROTEIN / protein complex |