ENVELOPE PROTEIN GP120
Human Immunodeficiency Virus type 1
Some viruses like the influenza virus have been around for a long time. In 1918 an influenza virus epidemic, known as the Spanish Influenza epidemic, killed an estimated 25 million people worldwide. Human immunodeficiency virus (HIV) is a very recently discovered virus, first identified in the USA in 1981. It is now commonly believed to have originated in Africa. The origin of HIV may be a related simian immuno- deficiency virus (SIV) which crossed the species from apes to humans and evolved into HIV. While not as infectious as for instance influenza virus, HIV has become a major health threat. HIV itself does not cause any harm. It does however weaken the immune system, hence its name. The immune system is the body's main defense against infections and a weakened immune system makes the body susceptible to infections that would otherwise be harmless. Such a situation is called Acquired Immune Deficiency Syndrome or AIDS. When an HIV-positive person gets AIDS, this person can die from even minor infections because the body can no longer defend itself against them. Like other viruses, HIV cannot reproduce by itself. HIV has a spherical shell, called the matrix. Inside this shell is a container called the capsid and inside this capsid is the viral RNA which contains HIV's genetic information. HIV is a so-called retrovirus, which means that it stores its genetic information not in DNA but RNA. The host cell then translates the RNA into DNA and that DNA is used for production of viral material. Obviously HIV has to get into the host cell and for this purpose it has surface proteins that help it to attach to the host cell. These proteins are embedded in a lipid membrane which surrounds the matrix. They consist of a stem protein, gp41, which sits inside the lipid membrane and, attached to gp41, the protein which binds to host cell surface receptors, a glycoprotein, gp120. The cells to which HIV attaches, are the T-helper cells of the immune system. These cells carry on their surface a protein called CD4 and gp120 binds to CD4 prior to entering the T-cell.
The structure shown here does not just show gp120 but a complex of three proteins: one is gp120, the other is CD4, whose structure was previously determined, also by Kwong and Hendrickson, and the third is the structure of a monoclonal antibody protein isolated from the blood of an HIV-infected person. It took several years of efforts by Peter Kwong to produce suitable crystals of gp120. Present drugs developed for treatment of HIV are targeted against the reproduction mechanism of HIV inside the host cell: drugs against the viral reverse transcriptase and against the viral protease. By studying the way gp120 binds to CD4 it is hoped that molecules can be found that prevent gp120 from binding to CD4. When that happens, HIV can no longer enter the host cell and since it needs the host cell for its own reproduction, will be prevented from spreading.
Protein Data Bank (PDB)
Kwong, P.D. Wyatt, R. Robinson, J. Sweet, R.W. Sodroski, J. Hendrickson, W.A.; "Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody."; Nature; (1998) 393:648-659 PubMed:9641677.
author: Arno Paehler