Nature: In the study of HIV, controversy has arisen over the architecture of certain glycoproteins, called HIV trimers, that form hook-like structures on the virus’s spherical surface. According to one study, the tip of the trimer’s spike has a cavity at its center, while another study says the spike harbors three helices, or corkscrew-shaped structures. Two subsequent studies appear to support the second finding. Ambiguity exists, however, because the proteins are so tiny and unstable that they are difficult to image. So far researchers have relied on cryo-electron microscopy, in which they introduce mutations to stabilize the proteins, freeze them with liquid nitrogen, and image thousands of randomly oriented copies. Statistical analysis is then used to extract a single, average image from the ensemble. However, the technique is vulnerable to artifacts because each individual image is fuzzy. Whether the differences in the findings are due to the technique's limitations, to the way the molecules were engineered for imaging, or to some other cause remains to be seen.
