Structure of key protein in HIV 'uncovered'

In addition, the scientists from California Institute of Technology demonstrated that a particular antibody to gp120 makes contact not only with the protein, but with 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, they say."There's a tremendous continuing effort to develop a vaccine for HIV and most of those efforts use gp120. Having more structural information will facilitate better vaccine design," said lead scientist Ron Diskin.

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," said Diskin. "It's the one that probably causes the largest number of infections worldwide." In order to uncover the structure of clade C gp120—and determine if the hypothesis about its similarities was indeed true—the Caltech team needed to crystallize the protein. That was no easy task. Turns out, says Diskin, the protein itself is not stiff enough for crystallization.

And so the researchers created a complex of molecules consisting of a gp120 monomer, a CD4 receptor, and an anti-HIV antibody known as 21c.

"The most interesting aspect of our structure is the unexpected contact between the antibody and CD4," says Pamela Bjorkman, the Max Delbruck Professor of Biology at Caltech, a Howard Hughes Medical Institute investigator, and the Caltech team's member.

"The binding to CD4 suggests that this class of anti-HIV antibodies has autoreactive properties, which raises many interesting questions about how anti-HIV immune responses affect an HIV-infected individual," she added.The findings have been published in the 'Nature Structural & Molecular Biology' journal.

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