6VKM

Crystal Structure of Stabilized GP from Makona Variant of Ebola Virus

Summary for 6VKM

• Entry DOI: 10.2210/pdb6vkm/pdb
• Descriptor: Virion spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: virus, glycoprotein, fusion, trimer, prefusion, ebov, viral protein
• Biological source: Zaire ebolavirus; More
• Total number of polymer chains: 1
• Total formula weight: 56092.06

Authors

Gilman, M.S.A.,Rutten, L.,Langedijk, J.P.M.,McLellan, J.S. (deposition date: 2020-01-21, release date: 2020-04-15, Last modification date: 2024-11-06)

Primary citation

Rutten, L.,Gilman, M.S.A.,Blokland, S.,Juraszek, J.,McLellan, J.S.,Langedijk, J.P.M.
Structure-Based Design of Prefusion-Stabilized Filovirus Glycoprotein Trimers.
Cell Rep, 30:4540-4550.e3, 2020

PubMed Abstract: Ebola virus causes severe hemorrhagic fever, often leading to death in humans. The trimeric fusion glycoprotein (GP) is the sole target for neutralizing antibodies and is the major focus of vaccine development. Soluble GP ectodomains are unstable and mostly monomeric when not fused to a heterologous trimerization domain. Here, we report structure-based designs of Ebola and Marburg GP trimers based on a stabilizing mutation in the hinge loop in refolding region 1 and substitution of a partially buried charge at the interface of the GP1 and GP2 subunits. The combined substitutions (T577P and K588F) substantially increased trimer expression for Ebola GP proteins. We determined the crystal structure of stabilized GP from the Makona Zaire ebolavirus strain without a trimerization domain or complexed ligand. The structure reveals that the stabilized GP adopts the same trimeric prefusion conformation, provides insight into triggering of GP conformational changes, and should inform future filovirus vaccine development.

PubMed: 32234486
DOI: 10.1016/j.celrep.2020.03.025

Experimental method

X-RAY DIFFRACTION (3.5 Å)