3VE0

Crystal structure of Sudan Ebolavirus Glycoprotein (strain Boniface) bound to 16F6

Summary for 3VE0

• Entry DOI: 10.2210/pdb3ve0/pdb
• Related: 3CSY 3S88
• Descriptor: Envelope glycoprotein, 16F6 Antibody chain A, 16F6 Antibody chain B, ... (5 entities in total)
• Functional Keywords: ebola, sudan, glycoprotein, virus surface, immune system-viral protein complex, immune system/viral protein
• Biological source: Sudan ebolavirus (SEBOV); More
• Cellular location: GP2: Virion membrane; Single-pass type I membrane protein (By similarity). GP1: Virion membrane; Peripheral membrane protein (By similarity). GP2-delta: Secreted (By similarity): Q66814 Q66814
• Total number of polymer chains: 4
• Total formula weight: 100470.29

Authors

Saphire, E.O.,Bale, S.,Dias, J.M. (deposition date: 2012-01-06, release date: 2012-04-18, Last modification date: 2023-09-13)

Primary citation

Bale, S.,Dias, J.M.,Fusco, M.L.,Hashiguchi, T.,Wong, A.C.,Liu, T.,Keuhne, A.I.,Li, S.,Woods, V.L.,Chandran, K.,Dye, J.M.,Saphire, E.O.
Structural basis for differential neutralization of ebolaviruses.
Viruses, 4:447-470, 2012

PubMed Abstract: There are five antigenically distinct ebolaviruses that cause hemorrhagic fever in humans or non-human primates (Ebola virus, Sudan virus, Reston virus, Taï Forest virus, and Bundibugyo virus). The small handful of antibodies known to neutralize the ebolaviruses bind to the surface glycoprotein termed GP₁,₂. Curiously, some antibodies against them are known to neutralize in vitro but not protect in vivo, whereas other antibodies are known to protect animal models in vivo, but not neutralize in vitro. A detailed understanding of what constitutes a neutralizing and/or protective antibody response is critical for development of novel therapeutic strategies. Here, we show that paradoxically, a lower affinity antibody with restricted access to its epitope confers better neutralization than a higher affinity antibody against a similar epitope, suggesting that either subtle differences in epitope, or different characteristics of the GP₁,₂ molecules themselves, confer differential neutralization susceptibility. Here, we also report the crystal structure of trimeric, prefusion GP₁,₂ from the original 1976 Boniface variant of Sudan virus complexed with 16F6, the first antibody known to neutralize Sudan virus, and compare the structure to that of Sudan virus, variant Gulu. We discuss new structural details of the GP₁-GP₂ clamp, thermal motion of various regions in GP₁,₂ across the two viruses visualized, details of differential interaction of the crystallized neutralizing antibodies, and their relevance for virus neutralization.

PubMed: 22590681
DOI: 10.3390/v4040447

Experimental method

X-RAY DIFFRACTION (3.353 Å)