Scientists have obtained the first high-resolution atomic structure of a receptor on T cells — the CCR5 receptor — that most HIV strains use to hijack the immune system. They also obtained structures of the receptor attached to the anti-retroviral drug, Maraviroc.
The team, from China and San Diego, published their findings Thursday in the journal Science.
HIV enters immune cells by binding to the surface receptor CD4. But it also needs to engage a co-receptor, which sits right next to CD4 in the membrane. For about 90 percent of HIV strains, that co-receptor is CCR5.
Genetic variations in a person’s CCR5 receptor can alter their risk for infection. This is most dramatically illustrated by people with a shortened version of the CCR5 receptor: A 32 base-pair deletion inactivates CCR5 and offers complete protection against HIV.
It took six years for the scientists to obtain a high-resolution, 3D model of CCR5. They hope this detailed blueprint of the receptor will make it easier to design better drugs to block HIV’s entry into T cells.
The illustration above shows the CCR5 receptor as a blue ribbon, with the anti-retroviral drug as orange and blue spheres. On the right hand side, you can see the CCR5 receptor modeled in the cell membrane and attached to a spike on the surface of an HIV particle.
Image courtesy of the Wu lab, SIMM