Biological processes involving movement, such as muscle contraction or the
opening of an ion channel through a membrane, are mediated through conforma
tional changes. These changes often occur in large and flexible macromolecu
lar complexes. Cryo-electron microscopy provides a means of capturing diffe
rent conformational states of such assemblies. Even if the resulting densit
y maps are at low resolution, they can be combined with atomic structures o
f subcomplexes or isolated components determined by X-ray crystallography o
r NMR. This review presents a brief summary of the principles and recent ad
vances in macromolecular structure determination by cryo-electron microscop
y.