5JNX

The 6.6 A cryo-EM structure of the full-length human NPC1 in complex with the cleaved glycoprotein of Ebola virus

Summary for 5JNX

• Entry DOI: 10.2210/pdb5jnx/pdb
• Related: 3JD8
• EMDB information: 8169
• Descriptor: Niemann-Pick C1 protein, Envelope glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: protein complex, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 7
• Total formula weight: 244801.86

Authors

Gong, X.,Qian, H.W.,Zhou, X.H.,Wu, J.P.,Wan, T.,Shi, Y.,Gao, F.,Zhou, Q.,Yan, N. (deposition date: 2016-05-01, release date: 2016-06-15, Last modification date: 2024-10-30)

Primary citation

Gong, X.,Qian, H.,Zhou, X.,Wu, J.,Wan, T.,Cao, P.,Huang, W.,Zhao, X.,Wang, X.,Wang, P.,Shi, Y.,Gao, G.F.,Zhou, Q.,Yan, N.
Structural Insights into the Niemann-Pick C1 (NPC1)-Mediated Cholesterol Transfer and Ebola Infection
Cell, 165:1467-1478, 2016

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. 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.

PubMed: 27238017
DOI: 10.1016/j.cell.2016.05.022

Experimental method

ELECTRON MICROSCOPY (6.56 Å)