Vaccination has been a successful strategy for protecting humans from many potentially harmful viruses. However, designing a suitable vaccine for HIV-1 has been a highly challenging and thus far unsuccessful endeavor. HIV-1 is enormously variable and it has been difficult to isolate antibodies that will recognize the many different strains of the virus. The antibody 4E10 was derived from HIV-1 infected patients by Dr. Hermann Katinger in Vienna and is the broadest acting neutralizing antibody against HIV-1 that is currently known. This antibody recognizes a protein called gp41 that is found on the surface of the virus. The gp41 protein is thought to play a key role in mediating entry of HIV-1 into human cells.
A research group led by Drs. Dennis R. Burton and Ian A. Wilson from The Scripps Research Institute in La Jolla, California performed a study examining the detailed molecular structure of the complex formed when 4E10 binds to gp41 and determining how interaction of 4E10 with gp41 influences the virus.
X-ray crystallography was used to determine the structure of the complex formed by association of 4E10 with a peptide fragment that is identical to the section of gp41 that the antibody recognizes. The researchers identified the specific amino acids on gp41 that 4E10 interacts with and the 3D structure adopted by these amino acids. These study results suggest that 4E10 interacts with gp41 at a conserved region very close to the surface of the virus and they reveal some special characteristics of 4E10 that make it unusually