Structural biology is a field that is many centuries old which, as defined by the Journal of Structural Biology, deals with structural analysis of living material at every level of organization. Early structural biologists throughout the 19th and early 20th centuries were primarily only able to study structures to the limit of the naked eye's visual acuity and through magnifying glasses and light microscopes.
Transmission electron cryomicroscopy (CryoTEM), commonly known as cryo-EM, is a form of cryogenic electron microscopy, more specifically a type of transmission electron microscopy (TEM) where the sample is studied at cryogenic temperatures. Cryo-EM is gaining popularity in structural biology.
Electron cryotomography (cryo-ET) is an imaging technique used to produce high-resolution (~1–4 nm) three-dimensional views of samples, often biological macromolecules and cells. cryo-ET is a specialized application of transmission electron cryomicroscopy (CryoTEM) in which samples are imaged as they are tilted, resulting in a series of 2D images that can be combined to produce a 3D reconstruction, similar to a CT scan of the human body. In contrast to other electron tomography techniques, samples are imaged under cryogenic conditions. For cellular material, the structure is immobilized in non-crystalline, vitreous ice, allowing them to be imaged without dehydration or chemical fixation, which would otherwise disrupt or distort biological structures.
MRC is a file format that has become an industry standard in cryo-electron microscopy (cryoEM) and electron tomography (ET), where the result of the technique is a three-dimensional grid of voxels each with a value corresponding to electron density or electric potential. It was developed by the MRC Laboratory of Molecular Biology. In 2014, the format was standardised. The format specification is available on the CCP-EM website.
Eva Nogales is a Spanish-American biophysicist at the Lawrence Berkeley National Laboratory and a professor at the University of California, Berkeley, where she served as head of the Division of Biochemistry, Biophysics and Structural Biology of the Department of Molecular and Cell Biology (2015–2020). She is a Howard Hughes Medical Institute investigator.
The EM Data Bank or Electron Microscopy Data Bank (EMDB) collects 3D EM maps and associated experimental data determined using electron microscopy of biological specimens. It was established in 2002 at the MSD/PDBe group of the European Bioinformatics Institute (EBI), where the European site of the EMDataBank.org consortium is located. As of 2015, the resource contained over 2,600 entries with a mean resolution of 15Å.
Ammonium heptamolybdate is the inorganic compound whose chemical formula is (NH4)6Mo7O24, normally encountered as the tetrahydrate. A dihydrate is also known. It is a colorless solid, often referred to as ammonium paramolybdate or simply as ammonium molybdate, although "ammonium molybdate" can also refer to ammonium orthomolybdate, (NH4)2MoO4, and several other compounds. It is one of the more common molybdenum compounds.
Resolution in terms of electron density is a measure of the resolvability in the electron density map of a molecule. In X-ray crystallography, resolution is the highest resolvable peak in the diffraction pattern, while resolution in cryo-electron microscopy is a frequency space comparison of two halves of the data, which strives to correlate with the X-ray definition.
In structural biology, as well as in virtually all sciences that produce three-dimensional data, the Fourier shell correlation (FSC) measures the normalised cross-correlation coefficient between two 3-dimensional volumes over corresponding shells in Fourier space (i.e., as a function of spatial frequency). The FSC is the three-dimensional extension of the two-dimensional Fourier ring correlation (FRC); also known as: spatial frequency correlation function.
Biology data visualization is a branch of bioinformatics concerned with the application of computer graphics, scientific visualization, and information visualization to different areas of the life sciences. This includes visualization of sequences, genomes, alignments, phylogenies, macromolecular structures, systems biology, microscopy, and magnetic resonance imaging data. Software tools used for visualizing biological data range from simple, standalone programs to complex, integrated systems.
Single particle analysis is a group of related computerized image processing techniques used to analyze images from transmission electron microscopy (TEM). These methods were developed to improve and extend the information obtainable from TEM images of particulate samples, typically proteins or other large biological entities such as viruses. Individual images of stained or unstained particles are very noisy, and so hard to interpret. Combining several digitized images of similar particles together gives an image with stronger and more easily interpretable features. An extension of this technique uses single particle methods to build up a three-dimensional reconstruction of the particle. Using cryo-electron microscopy it has become possible to generate reconstructions with sub-nanometer resolution and near-atomic resolution first in the case of highly symmetric viruses, and now in smaller, asymmetric proteins as well. Single particle analysis can also be performed by induced coupled plasma mass spectroscopy (ICP-MS).
The term macromolecular assembly (MA) refers to massive chemical structures such as viruses and non-biologic nanoparticles, cellular organelles and membranes and ribosomes, etc. that are complex mixtures of polypeptide, polynucleotide, polysaccharide or other polymeric macromolecules. They are generally of more than one of these types, and the mixtures are defined spatially, and with regard to their underlying chemical composition and structure. Macromolecules are found in living and nonliving things, and are composed of many hundreds or thousands of atoms held together by covalent bonds; they are often characterized by repeating units. Assemblies of these can likewise be biologic or non-biologic, though the MA term is more commonly applied in biology, and the term supramolecular assembly is more often applied in non-biologic contexts. MAs of macromolecules are held in their defined forms by non-covalent intermolecular interactions, and can be in either non-repeating structures, or in repeating linear, circular, spiral, or other patterns. The process by which MAs are formed has been termed molecular self-assembly, a term especially applied in non-biologic contexts. A wide variety of physical/biophysical, chemical/biochemical, and computational methods exist for the study of MA; given the scale of MAs, efforts to elaborate their composition and structure and discern mechanisms underlying their functions are at the forefront of modern structure science.
Ueli Aebi is a Swiss structural biologist and co-founder of the Maurice E. Müller Institute for Structural Biology at the Biozentrum University of Basel.
Jacques Dubochet is a retired Swiss biophysicist. He is a former researcher at the European Molecular Biology Laboratory in Heidelberg, Germany, and an honorary professor of biophysics at the University of Lausanne in Switzerland.
Cryogenic electron microscopy (cryo-EM) is a cryomicroscopy technique applied on samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An aqueous sample solution is applied to a grid-mesh and plunge-frozen in liquid ethane or a mixture of liquid ethane and propane. While development of the technique began in the 1970s, recent advances in detector technology and software algorithms have allowed for the determination of biomolecular structures at near-atomic resolution. This has attracted wide attention to the approach as an alternative to X-ray crystallography or NMR spectroscopy for macromolecular structure determination without the need for crystallization.
Lori Anne Passmore is a Canadian/British cryo electron microscopist and structural biologist who works at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) at the University of Cambridge. She is known for her work on multiprotein complexes involved in gene expression and development of new supports for cryo-EM.
Tamir Gonen is an American structural biochemist and membrane biophysicist best known for his contributions to structural biology of membrane proteins, membrane biochemistry and electron cryo-microscopy (cryoEM) particularly in electron crystallography of 2D crystals and for the development of 3D electron crystallography from microscopic crystals known as MicroED. Gonen is an Investigator of the Howard Hughes Medical Institute, a professor at the University of California, Los Angeles, the founding director of the MicroED Imaging Center at UCLA and a Member of the Royal Society of New Zealand.
Sjors Hendrik Willem ScheresFRS is a Dutch scientist at the MRC Laboratory of Molecular Biology Cambridge, UK.
Microcrystal electron diffraction, or MicroED, is a CryoEM method that was developed by the Gonen laboratory in late 2013 at the Janelia Research Campus of the Howard Hughes Medical Institute. MicroED is a form of electron crystallography where thin 3D crystals are used for structure determination by electron diffraction. Prior to this demonstration, macromolecular (protein) electron crystallography was only used on 2D crystals, for example.
Kiyoshi Nagai was a Japanese structural biologist at the MRC Laboratory of Molecular Biology Cambridge, UK. He was known for his work on the mechanism of RNA splicing and structures of the spliceosome.
