"Structure
of an HIV gp120 envelope glycoprotein in complex
with
the CD4 receptor and a neutralizing human antibody"
by: Peter D. Kwong, Richard Wyatt, James
Robinson, Raymond W. Sweet, Joeseph Sodroski, and Wayne A. Hendrickson
In this paper the researchers were attempting
to discover more about how the gp120 glycoprotein
of HIV binds to the CD4 glycoprotien of a host
cell. To first discover the structure of gp120 and how the virus
binds to a normal cell, the group used a method called x-ray crystallography.
X-ray crystallography is the best way to determine protein structure at
the atomic level. This method creates a short wavelength to allow
the viewing of things that are very closer together. After performing
this experiment the group found that their theory about gp120 binding to
the CD4 receptor was correct. They also found more extensive data
about bindings induced from the initial binding of CD4.
A detailed description
of the research results
Acquired immunodeficiency syndrome (AIDS)
is caused by the human immunodeficiency virus (HIV) which destroys the
CD4 lymphocytes of the host. HIV enters
the host cell by way of its viral envelope of glycoproteins. On the
surface of the HIV virus, the exterior envelope glycoprotein is gp120 which
binds to its primary receptor, the CD4 glycoprotein, on the host cell.
The binding of these two induces conformational
changes in the structure of gp120. One of the conformational
changes is the formation of the Phe 43 cavity (a
pocket). An antibody named Fab
17b, from the blood of an HIV infected individual, binds to the CD4-induced
gp120 epitope. The 17b epitope lies over
the base of the four stranded bridging sheet of the gp120. Since
each of these strands makes contact with 17b it suggests that the bridging
sheet is necessary for 17b binding. CD4-induced conformational change
is thought to protect the 17b epitope from the immune system. After
the Phe 43 cavity forms and binds with the 17b epitope, the chemokine receptor
binds to the bridging sheet and the V3 loop of the gp120. The interactions
between the acidic chemokine receptor and the basic surface of the bridging
sheet could possibly drive further conformational changes which relate
to virus entry.
A more general
description of how gp120 binds to CD4
The diagram below is representational of what
occurs when gp120 binds to CD4 and
then binds to the chemokine receptor. As described above the first
main conformational change in the structure of gp120 is the formation of
the Phe43 cavity.
In this case the V1/V2
loops of gp120 move aside to allow the
formation of this cavity. Once this cavity has formed it binds with
the Fab 17b epitope of the human antibody. This allows for the binding
of the chemokine receptor to the V3 loop
and the bridging sheet. With each consecutive binding, gp120 becomes
more solidly attached to the host cell. Further conformational changes
eventually allow the HIV virus to inject its genetic material into the
cell.
Group 2
The Biology Project
University of Arizona
Tucson, AZ. 85719