3VE0: Crystal Structure Of Sudan Ebolavirus Glycoprotein (Strain Boniface) Bound To 16f6

Citation:
Abstract
There are five antigenically distinct ebolaviruses that cause hemorrhagic fever in humans or non-human primates (Ebola virus, Sudan virus, Reston virus, Tai Forest virus, and Bundibugyo virus). The small handful of antibodies known to neutralize the ebolaviruses bind to the surface glycoprotein termed GP(1,2). 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 GP(1,2) molecules themselves, confer differential neutralization susceptibility. Here, we also report the crystal structure of trimeric, prefusion GP(1,2) 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 GP(1)-GP(2) clamp, thermal motion of various regions in GP(1,2) across the two viruses visualized, details of differential interaction of the crystallized neutralizing antibodies, and their relevance for virus neutralization.
PDB ID: 3VE0Download
MMDB ID: 98846
PDB Deposition Date: 2012/1/6
Updated in MMDB: 2012/05
Experimental Method:
x-ray diffraction
Resolution: 3.35  Å
Source Organism:
Sudan virus - Boniface, Sudan,1976
Similar Structures:
Biological Unit for 3VE0: tetrameric; determined by author and by software (PISA)
Molecular Components in 3VE0
Label Count Molecule
Proteins (4 molecules)
1
Envelope Glycoprotein
Molecule annotation
1
Envelope Glycoprotein
Molecule annotation
1
16f6 Antibody Chain a
Molecule annotation
1
16f6 Antibody Chain B
Molecule annotation
Chemicals (6 molecules)
1
4
2
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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