PASADENA, Calif.Scientists from the California Institute of Technology (Caltech) have provided the first-ever glimpse of the structure of a key proteingp120found on the surface of a specific subgroup of the human immunodeficiency virus, HIV-1. In addition, they demonstrated that a particular antibody to gp120 makes contact not only with the protein, but with the CD4 receptor that gp120 uses to gain entrance into the body's T cells.
This three-dimensional understanding of how gp120 is built is more than just a basic scientific advance. "There's a tremendous continuing effort to develop a vaccine for HIV," says Caltech postdoctoral scholar Ron Diskin, "and most of those efforts use gp120. Having more structural information will facilitate better vaccine design."
The findings are detailed in a paper published in the advance online edition of the journal Nature Structural & Molecular Biology.
The team looked specifically at gp120 from what is known as clade C HIV-1. To explain what that means, here's a brief HIV family history: Most people who get HIV and proceed to AIDS are infected with a member of the HIV-1 family of viruses. HIV-1 is divided into groups; most AIDS-related strains of the virus come from group M. The groups are further subdivided into what are known as clades.
Clade B is the form of group M HIV-1 most often found in the United States and western Europe, and the one that is probably best-studied to date. Clade C, the clade studied by the Caltech team, is "the one that is devastating Africa and Asia," says Diskin. "It's the one that probably causes the largest number of infections worldwide."
Previous studies had looked at the structure of clade B gp120, and it had been assumedbut not proventhat clade C's version would look much the same.
In order to uncover the structure of clade C gp120and determine if the hypothesis about its similarities was indeed truethe Caltech team needed to c
|Contact: Lori Oliwenstein|
California Institute of Technology