5HJ3

Crystal structure of host-primed Ebola virus GP, GPcl.

Summary for 5HJ3

• Entry DOI: 10.2210/pdb5hj3/pdb
• Descriptor: Envelope glycoprotein, KZ52 Antibody Fragment, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: ebola virus, eov, ebolavirus, gp, glycoprotein, gpcl, cleaved, primed, proteolytically, receptor binding pocket, crest, trough, mr72, kz52, broadly neutralizing, viral protein-immune system complex, viral protein/immune system
• Biological source: Ebola virus sp.; More
• Cellular location: GP2: Virion membrane ; Single-pass type I membrane protein . GP1: Virion membrane ; Peripheral membrane protein. GP2-delta: Secreted : Q05320 P87666
• Total number of polymer chains: 16
• Total formula weight: 336368.72

Authors

Bornholdt, Z.A.,Fusco, M.L.,Saphire, E.O. (deposition date: 2016-01-12, release date: 2016-03-09, Last modification date: 2024-10-30)

Primary citation

Bornholdt, Z.A.,Ndungo, E.,Fusco, M.L.,Bale, S.,Flyak, A.I.,Crowe, J.E.,Chandran, K.,Saphire, E.O.
Host-Primed Ebola Virus GP Exposes a Hydrophobic NPC1 Receptor-Binding Pocket, Revealing a Target for Broadly Neutralizing Antibodies.
Mbio, 7:e02154-e02115, 2016

PubMed Abstract: The filovirus surface glycoprotein (GP) mediates viral entry into host cells. Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS) that is otherwise hidden from immune surveillance. Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å. We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution. Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP1 subunit. Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics.

PubMed: 26908579
DOI: 10.1128/mBio.02154-15

Experimental method

X-RAY DIFFRACTION (3.3 Å)