Visualizing flexibility at molecular resolution: analysis of heterogeneity in single-particle electron microscopy reconstructions.
It is becoming increasingly clear that many macromolecules are intrinsically flexible and exist in multiple conformations in solution. Single-particle reconstruction of vitrified samples (cryo-electron microscopy, or cryo-EM) is uniquely positioned to visualize this conformational flexibility in its native state. Although heterogeneity remains a significant challenge in cryo-EM single-particle analysis, recent efforts in the field point to a future where it will be possible to tap into this rich source of biological information on a routine basis. In this article, we review the basic principles behind a few relatively new and generally applicable methods that show particular promise as tools to analyze macromolecular flexibility. We also discuss some of their recent applications to problems of biological interest.
Leschziner
Andres E
AE
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA. aeleschziner@berkeley.edu
Nogales
Eva
E
D000818:Animals; D001703:Biophysics / Q000379:methods*; D020285:Cryoelectron Microscopy / Q000379:methods*; D004926:Escherichia coli / Q000378:metabolism; D005583:Fourier Analysis; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D016013:Likelihood Functions; D046911:Macromolecular Substances; D008968:Molecular Conformation; D009991:Oscillometry; D012270:Ribosomes / Q000737:chemistry
D046911:Macromolecular Substances