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| 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 |
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Keywords | MEMBRANE PROTEIN / protein complex |
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homo sapiens (human)
ebola virus - zaire (1995)
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