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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 (i.e., with regard to their chemical shape), 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 (i.e., they are polymers). 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 (e.g., in supramolecular chemistry and nanotechnology). MAs of macromolecules are held in their defined forms by non-covalent intermolecular interactions (rather than covalent bonds), and can be in either non-repeating structures (e.g., as in the ribosome (image) and cell membrane architectures), or in repeating linear, circular, spiral, or other patterns (e.g., as in actin filaments and the flagellar motor, image). 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 (molecular dimensions) of MAs, efforts to elaborate their composition and structure and discern mechanisms underlying their functions are at the forefront of modern structure science.
A biomolecular complex, also called a biomacromolecular complex, is any biological complex made of more than one biopolymer (protein, RNA, DNA, [5] carbohydrate) or large non-polymeric biomolecules (lipid). The interactions between these biomolecules are non-covalent. [6] Examples:
The biomacromolecular complexes are studied structurally by X-ray crystallography, NMR spectroscopy of proteins, cryo-electron microscopy and successive single particle analysis, and electron tomography. [9] The atomic structure models obtained by X-ray crystallography and biomolecular NMR spectroscopy can be docked into the much larger structures of biomolecular complexes obtained by lower resolution techniques like electron microscopy, electron tomography, and small-angle X-ray scattering. [10]
Complexes of macromolecules occur ubiquitously in nature, where they are involved in the construction of viruses and all living cells. In addition, they play fundamental roles in all basic life processes (protein translation, cell division, vesicle trafficking, intra- and inter-cellular exchange of material between compartments, etc.). In each of these roles, complex mixtures of become organized in specific structural and spatial ways. While the individual macromolecules are held together by a combination of covalent bonds and intramolecular non-covalent forces (i.e., associations between parts within each molecule, via charge-charge interactions, van der Waals forces, and dipole–dipole interactions such as hydrogen bonds), by definition MAs themselves are held together solely via the noncovalent forces, except now exerted between molecules (i.e., intermolecular interactions).[ citation needed ]
The images above give an indication of the compositions and scale (dimensions) associated with MAs, though these just begin to touch on the complexity of the structures; in principle, each living cell is composed of MAs, but is itself an MA as well. In the examples and other such complexes and assemblies, MAs are each often millions of daltons in molecular weight (megadaltons, i.e., millions of times the weight of a single, simple atom), though still having measurable component ratios (stoichiometries) at some level of precision. As alluded to in the image legends, when properly prepared, MAs or component subcomplexes of MAs can often be crystallized for study by protein crystallography and related methods, or studied by other physical methods (e.g., spectroscopy, microscopy).[ citation needed ]
Virus structures were among the first studied MAs; other biologic examples include ribosomes (partial image above), proteasomes, and translation complexes (with protein and nucleic acid components), procaryotic and eukaryotic transcription complexes, and nuclear and other biological pores that allow material passage between cells and cellular compartments. Biomembranes are also generally considered MAs, though the requirement for structural and spatial definition is modified to accommodate the inherent molecular dynamics of membrane lipids, and of proteins within lipid bilayers. [15]
During assembly of the bacteriophage (phage) T4 virion, the morphogenetic proteins encoded by the phage genes interact with each other in a characteristic sequence. Maintaining an appropriate balance in the amounts of each of these proteins produced during viral infection appears to be critical for normal phage T4 morphogenesis. [16] Phage T4 encoded proteins that determine virion structure include major structural components, minor structural components and non-structural proteins that catalyze specific steps in the morphogenesis sequence [17]
The study of MA structure and function is challenging, in particular because of their megadalton size, but also because of their complex compositions and varying dynamic natures. Most have had standard chemical and biochemical methods applied (methods of protein purification and centrifugation, chemical and electrochemical characterization, etc.). In addition, their methods of study include modern proteomic approaches, computational and atomic-resolution structural methods (e.g., X-ray crystallography), small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS), force spectroscopy, and transmission electron microscopy and cryo-electron microscopy. Aaron Klug was recognized with the 1982 Nobel Prize in Chemistry for his work on structural elucidation using electron microscopy, in particular for protein-nucleic acid MAs including the tobacco mosaic virus (a structure containing a 6400 base ssRNA molecule and >2000 coat protein molecules). The crystallization and structure solution for the ribosome, MW ~ 2.5 MDa, an example of part of the protein synthetic 'machinery' of living cells, was object of the 2009 Nobel Prize in Chemistry awarded to Venkatraman Ramakrishnan, Thomas A. Steitz, and Ada E. Yonath. [18]
Finally, biology is not the sole domain of MAs. The fields of supramolecular chemistry and nanotechnology each have areas that have developed to elaborate and extend the principles first demonstrated in biologic MAs. Of particular interest in these areas has been elaborating the fundamental processes of molecular machines, and extending known machine designs to new types and processes.[ citation needed ]
In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name organelle comes from the idea that these structures are parts of cells, as organs are to the body, hence organelle, the suffix -elle being a diminutive. Organelles are either separately enclosed within their own lipid bilayers or are spatially distinct functional units without a surrounding lipid bilayer. Although most organelles are functional units within cells, some function units that extend outside of cells are often termed organelles, such as cilia, the flagellum and archaellum, and the trichocyst.
Ribosomes are macromolecular machines, found within all cells, that perform biological protein synthesis. Ribosomes link amino acids together in the order specified by the codons of messenger RNA molecules to form polypeptide chains. Ribosomes consist of two major components: the small and large ribosomal subunits. Each subunit consists of one or more ribosomal RNA molecules and many ribosomal proteins. The ribosomes and associated molecules are also known as the translational apparatus.
Structural biology, 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.
Biophysics is an interdisciplinary science that applies approaches and methods traditionally used in physics to study biological phenomena. Biophysics covers all scales of biological organization, from molecular to organismic and populations. Biophysical research shares significant overlap with biochemistry, molecular biology, physical chemistry, physiology, nanotechnology, bioengineering, computational biology, biomechanics, developmental biology and systems biology.
Peripheral membrane proteins, or extrinsic membrane proteins, are membrane proteins that adhere only temporarily to the biological membrane with which they are associated. These proteins attach to integral membrane proteins, or penetrate the peripheral regions of the lipid bilayer. The regulatory protein subunits of many ion channels and transmembrane receptors, for example, may be defined as peripheral membrane proteins. In contrast to integral membrane proteins, peripheral membrane proteins tend to collect in the water-soluble component, or fraction, of all the proteins extracted during a protein purification procedure. Proteins with GPI anchors are an exception to this rule and can have purification properties similar to those of integral membrane proteins.
Kurt Wüthrich is a Swiss chemist/biophysicist and Nobel Chemistry laureate, known for developing nuclear magnetic resonance (NMR) methods for studying biological macromolecules.
Structural bioinformatics is the branch of bioinformatics that is related to the analysis and prediction of the three-dimensional structure of biological macromolecules such as proteins, RNA, and DNA. It deals with generalizations about macromolecular 3D structures such as comparisons of overall folds and local motifs, principles of molecular folding, evolution, binding interactions, and structure/function relationships, working both from experimentally solved structures and from computational models. The term structural has the same meaning as in structural biology, and structural bioinformatics can be seen as a part of computational structural biology. The main objective of structural bioinformatics is the creation of new methods of analysing and manipulating biological macromolecular data in order to solve problems in biology and generate new knowledge.
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, specifically 3-dimensional electron microscopy (3DEM), is gaining popularity in structural biology.
Cryogenic electron tomography (cryoET) is an imaging technique used to reconstruct high-resolution (~1–4 nm) three-dimensional volumes of samples, often biological macromolecules and cells. cryoET 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.
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.
Roger David Kornberg is an American biochemist and professor of structural biology at Stanford University School of Medicine. Kornberg was awarded the Nobel Prize in Chemistry in 2006 for his studies of the process by which genetic information from DNA is copied to RNA, "the molecular basis of eukaryotic transcription."
Molecular biophysics is a rapidly evolving interdisciplinary area of research that combines concepts in physics, chemistry, engineering, mathematics and biology. It seeks to understand biomolecular systems and explain biological function in terms of molecular structure, structural organization, and dynamic behaviour at various levels of complexity. This discipline covers topics such as the measurement of molecular forces, molecular associations, allosteric interactions, Brownian motion, and cable theory. Additional areas of study can be found on Outline of Biophysics. The discipline has required development of specialized equipment and procedures capable of imaging and manipulating minute living structures, as well as novel experimental approaches.
The following outline is provided as an overview of and topical guide to cell biology:
Resolution in the context of structural biology is the ability to distinguish the presence or absence of atoms or groups of atoms in a biomolecular structure. Usually, the structure originates from methods such as X-ray crystallography, electron crystallography, or cryo-electron microscopy. The resolution is measured of the "map" of the structure produced from experiment, where an atomic model would then be fit into. Due to their different natures and interactions with matter, in X-ray methods the map produced is of the electron density of the system, whereas in electron methods the map is of the electrostatic potential of the system. In both cases, atomic positions are assumed similarly.
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.
Biophysical chemistry is a physical science that uses the concepts of physics and physical chemistry for the study of biological systems. The most common feature of the research in this subject is to seek an explanation of the various phenomena in biological systems in terms of either the molecules that make up the system or the supra-molecular structure of these systems. Apart from the biological applications, recent research showed progress in the medical field as well.
Food physical chemistry is considered to be a branch of Food chemistry concerned with the study of both physical and chemical interactions in foods in terms of physical and chemical principles applied to food systems, as well as the applications of physical/chemical techniques and instrumentation for the study of foods. This field encompasses the "physiochemical principles of the reactions and conversions that occur during the manufacture, handling, and storage of foods."
Joachim Frank ; born September 12, 1940) is a German-American biophysicist at Columbia University and a Nobel laureate. He is regarded as the founder of single-particle cryo-electron microscopy (cryo-EM), for which he shared the Nobel Prize in Chemistry in 2017 with Jacques Dubochet and Richard Henderson. He also made significant contributions to structure and function of the ribosome from bacteria and eukaryotes.
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.