Work

Cryo-EM of viruses and vaccine design

Year: 2016

Type: article

Abstract: Knowledge of the atomic resolution structures of viruses can be a powerful tool for vaccine discovery and design. X-ray crystallography has long served as an invaluable method for virus structure determination at high resolution, but over the past decade, cryo-electron microscopy (cryo-EM) has begun to emerge as a complementary method that can also provide this kind of information. Crystallographic approaches require significant amounts of purified virus that is structurally homogeneous. In instances where production of adequate amounts of purified virus can be challenging, or where homogeneity is difficult to achieve, the use of cryo-EM and image averaging may be the only way to obtain structural information at high resolution. In PNAS, Rossmann and co-workers (1) use cryo-EM techniques to present elegant results on the structure determination of rhinovirus C, a strain of rhinovirus that is associated with severe disease in children with asthma (2). Rhinoviruses of A, B, and C categories are the leading cause of common colds; there are well over 100 of these types of viruses. Efforts to understand the molecular mechanism of cell receptor binding and differences between rhinovirus strains have been hampered by the lack of structural information, especially for those strains that are difficult to propagate in cell culture (3). It was almost two decades ago that the first breakthroughs were made in the use of cryo-EM for virus structure determination, with the report of structures at ∼7 A resolution of the hepatitis B capsid (4, 5). A decade later, the first near-atomic resolution maps of icosahedral viruses, derived solely from cryo-EM, were published (6, 7). Since that time, as methods for high-resolution cryo-EM have become more widely used, dozens of near-atomic resolution structures of icosahedral viruses have been deposited in the Electron Microscopy Data Bank … [↵][1]1To whom correspondence should be addressed. Email: ss1{at}nih.gov. [1]: #xref-corresp-1-1

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1609721113

Authors: Lesley A. Earl, Sriram Subramaniam

Institutions: National Institutes of Health, National Cancer Institute, Center for Cancer Research

Language: English

Topic: Advanced Electron Microscopy Techniques and Applications

Subfield: Structural Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Cancer Institute