The Pittsburg High School SMART Team studied the crystal structure of the Ebola virus glycoprotein (GP) bound to a human survivor antibody. GP consists of two subunits, GP1 and GP2, and mediates host cell attachment and entry. The crystal structure revealed that three GP1 subunits are cradled by GP2 helices in a bowl shape, with the receptor-binding site inside. Three antibody units bind tightly to GP2 via interactions that prevent GP2 from rearranging into its fusion form, neutralizing the virus. Understanding this structure may help develop effective vaccines against Ebola by inhibiting GP's role in the viral life cycle.

1. Pittsburg High School SMART Team
Student: Adrian McAfee
Teacher: James Foresman
Mentor: Irene Zegar
The Ebola Virus Glycoprotein:An Essential Envelope Protein for the Life Cycle of
Ebola Virus
PDB ID: 3CSY.pdb
Primary Citation: Lee J. E., Fusco, M. L., Hessell, A. J., Oswald, W. B., Burton, D. R., and
Saphire, E. O. (2008) Structure of the Ebola virus glycoprotein bound to a human survivor
antibody. Nature, 454(7201): 177-182.
Secondary Citation: BBC News Africa, (12 December, 2014). Retrieved from:
http://www.bbc.com/news/world-africa-28755033
Abstract:
The recent Ebola virus outbreak, which has claimed the lives of thousands of people worldwide,
can be traced to a two-year old boy from Guinea who died shortly after contracting the virus.
This disease is associated with a severe hemorrhagic fever with a mortality rate of 50-90%.
Currently, FDA-approved vaccines for humans are nonexistent, which is due, in part, to the
virus’s high replication rate leading to a breakdown in the host immune defenses. The Ebola
viral envelope Glycoprotein (GP) consists of two subunits, GP1 and GP2, and is believed to
mediate host recognition, attachment to and entry into the host cell as well as provide protection
from immune defenses. A pre-fusion crystal structure of GP bound to a human survivor antibody
reveals that the three GP1 subunits are cradled by the helices of GP2 and form a bowl
shaped trimer of GP1-GP2 dimers within which the putative receptor-binding site is thought to
reside. This is in contrast to the anti-parallel six-helical bundle that GP2 adopts in its fusion
form. The crystal structure also reveals that three antibody units form multiple van der Waals
and hydrogen bonding interactions to the GP2 subunits of the trimer. Insight into the structure
suggests that the neutralization activity of the antibody results from its tight binding to GP2, thus
preventing GP2 from rearranging to its fusion form. The Pittsburg High School SMART TEAM
used 3D technology to design the Ebola virus GP bound to a human survivor antibody in order
to understand the link between its structure and the role it plays in the life cycle of the virus. It
is believed that new insights gained from this and other related structures will facilitate the
development of effective vaccines against this deadly virus.