2013/10/30
Structural virology: making an impact in biology through hybrid methods
The study of virus structures has contributed to structure biology methodological advances that go beyond virus-specific methods and are generally applicable (molecular replacement and non-crystallographic symmetry are only two of the best known examples). Moreover, structural virology has been instrumental in forging the more general concept of exploiting phase information derived from multiple structural techniques. This hybridization of structural methods, primarily electron microscopy (EM) and X-ray crystallography, but also small-angle X-ray scattering (SAXS) and nuclear magnetic resonance (NMR) spectroscopy, is central to integrative structural biology.
In this article, the interplay of X-ray crystallography and EM is illustrated through the example of the structural determination of the marine lipid-containing bacteriophage PM2. Molecular replacement starting from an ~13 Å cryo-EM reconstruction, followed by cycling density averaging, phase extension and solvent flattening, gave the X-ray structure of the intact virus at 7 Å resolution. This in turn served as a bridge to phase, to 2.5 Å resolution, data from twinned crystals of the major coat protein (P2), ultimately yielding a quasi-atomic model of the particle, which provided significant insights into virus evolution and viral membrane biogenesis.
Bibliographical references for the study:
From lows to highs: using low-resolution models to phase X-ray data
D. I. Stuart and N. G. A. Abrescia
Acta Cryst. (2013). D69, 2257-2265
http://journals.iucr.org/d/issues/2013/11/00/ba5207/index.html
Nicola G.A. Abrescia is an Ikerbasque Research Professor and Group Leader at the Structural Biology Unit at CIC bioGUNE. His research focuses on the structural study of large and complex macromolecular assemblies using hybridization of methods such as electron microscopy and X-ray crystallography techniques, with a special emphasis on viruses with a membrane.
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