3.8 Molecular Dynamics of Membrane Protein and Receptor Protein Binding
Collaborators : Christina Vasilakis (University of Illinois at Chicago),
Edwin Westbrook (Argonne National Laboratory).
The cholera toxin is a mysterious and, until recently, elusive
macromolecule which has infected and killed people for
the past 150 years. Treatment of cholera would be aided by a thorough understanding of
the mechanisms by which the toxin infects and quickly destroys a
membrane. In order to begin to tackle this question, the
structure of the bacterial protein must be solved [gibbsons]. Edwin Westbrook, our collaborator
in this project, is one of the pioneers in solving the structure of
the cholera toxin. His research results describe the cholera toxin structure
and its dynamics. Still unsolved however is the problem of how the cholera toxin invades
the external membrane of a healthy cell.
3.8.1 CAVE Visualization
This project uses the CAVE as a visualization tool to gain an understanding
of the how the cholera toxin invades the cell's membrane. The application depicts
a possible theory of how the cholera toxin transports an intact protein
through a target cell's external membrane while intoxicating the cell. The cholera
toxin is represented in terms of two basic structures: a red donut-shaped unit
representing the receptor binding domain and a smaller yellow drop-shaped unit
representing the active toxine enzyme. Figure 10 shows the cholera structure
and the cell membrane. The colors are arbitrary and help the viewer distinguish
between the two main components.
figure 10
The CAVE viewer witnesses the two stage process of the infection of a
membrane. The first stage, the recognition process, occurs when the
toxin approaches the target cell and finds a place where it can
successfully attach itself, as can be seen in Figure 11. Once the molecule has ``docked'',
it begins the second and lethal stage of infection by penetration. Once
the yellow enzyme is inside the cell, a chain of events is fired, which will
lead to dehydration and eventually death of the infected person.
figure 11
3.8.2 Discussion
This view of the transportation of the cholera toxin can be studied from a new
and otherwise not so easily accessible point of view by virtue of the
CAVE. The viewers can walk around the target area of the membrane and
examine it. They can also experience the entire two stage process
described above by walking around the target area, watching the
binding domain approach the cell layer, and especially by peering
through the hole through which the toxin penetrates and enters the
cell membrane. The viewer can watch the entire process from either
above or below the membrane, or even stand in the middle of it. The
most common way viewers watched the simulation at the SIGGRAPH'92
conference was by alternating the views from
above and below the membrane. They also reported that, in this way,
they most strongly experienced the three dimensionality of the
structures.
NEXT PAGE
Applications MENU
Scientists in Wonderland
MENU