title: Cryo-electron microscopy--a primer for the non-microscopist.
abstract: Cryo-electron microscopy (cryo-EM) is increasingly becoming a mainstream technology for studying the architecture of cells, viruses and protein assemblies at molecular resolution. Recent developments in microscope design and imaging hardware, paired with enhanced image processing and automation capabilities, are poised to further advance the effectiveness of cryo-EM methods. These developments promise to increase the speed and extent of automation, and to improve the resolutions that may be achieved, making this technology useful to determine a wide variety of biological structures. Additionally, established modalities for structure determination, such as X-ray crystallography and nuclear magnetic resonance spectroscopy, are being routinely integrated with cryo-EM density maps to achieve atomic-resolution models of complex, dynamic molecular assemblies. In this review, which is directed towards readers who are not experts in cryo-EM methodology, we provide an overview of emerging themes in the application of this technology to investigate diverse questions in biology and medicine. We discuss the ways in which these methods are being used to study structures of macromolecular assemblies that range in size from whole cells to small proteins. Finally, we include a description of how the structural information obtained by cryo-EM is deposited and archived in a publicly accessible database.
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jacqueline L S
authors.initials: JL
authors.lastname: Milne
authors.forename: Mario J
authors.initials: MJ
authors.lastname: Borgnia
authors.forename: Alberto
authors.initials: A
authors.lastname: Bartesaghi
authors.forename: Erin E H
authors.initials: EE
authors.lastname: Tran
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Earl
authors.forename: David M
authors.initials: DM
authors.lastname: Schauder
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lengyel
authors.forename: Jason
authors.initials: J
authors.lastname: Pierson
authors.forename: Ardan
authors.initials: A
authors.lastname: Patwardhan
authors.forename: Sriram
authors.initials: S
authors.lastname: Subramaniam
mesh_terms: D000818:Animals; D020285:Cryoelectron Microscopy / Q000379:methods*; D055032:Electron Microscope Tomography; D005583:Fourier Analysis; D006801:Humans; D021621:Imaging, Three-Dimensional; D046911:Macromolecular Substances / Q000648:ultrastructure; D011506:Proteins / Q000648:ultrastructure
chemical_list: D046911:Macromolecular Substances; D011506:Proteins