HIV and influenza share a similar structural blueprint
To infect cells, the human immunodeficiency virus (HIV) uses a protein called the envelope glycoprotein spike to attach itself and fuse with the cell membrane; NCI scientists have now defined the structure of this spike in its pre-fusion state using cryo-electron microscopy. New experiments show that the spike is held together by a bundle of three alpha-helices (protein segments). When the spike is bound to receptors on the cell’s surface and becomes activated the outer portions of the spike swivel away from the helix bundle. This rearrangement allows the spike to begin the process of HIV infection. This model for the activation of the HIV spike is similar to that of other enveloped viruses such as influenza. The surprising correlation between these viruses may open new avenues of investigation for researchers developing novel treatments.
This research, conducted by Sriram Subramaniam, Ph.D., Center for Cancer Research, NCI, and colleagues, appeared Oct. 23, 2013, in Nature Structural and Molecular Biology. While past insights into the molecular structure of influenza spikes came mainly from X-ray crystallography, Subramaniam and his team have used cryo-electron microscopy to determine the structures of both the pre-fusion and activated states in their research on the HIV spike. These researchers are also using cryo-electron microscopy to understand how various multi-protein complexes important for cell signaling and metabolism are assembled and how these complexes are altered in diseases such as cancer.
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