Structural biology
Encyclopedia
Structural biology is a branch of molecular biology
, biochemistry
, and biophysics
concerned with the molecular structure of biological macromolecule
s, especially protein
s and nucleic acid
s, how they acquire the structures they have, and how alterations in their structures affect their function. This subject is of great interest to biologists because macromolecules carry out most of the functions of cells
, and because it is only by coiling into specific three-dimensional shapes that they are able to perform these functions. This architecture, the "tertiary structure
" of molecules, depends in a complicated way on the molecules' basic composition, or "primary structure
s."
Biomolecule
s are too small to see in detail even with the most advanced light microscope
s. The methods that structural biologists use to determine their structures generally involve measurements on vast numbers of identical molecules at the same time. These methods include:
Most often researchers use them to study the static "native state
s" of macromolecules. But variations on these methods are also used to watch nascent or denatured
molecules assume or reassume their native states. See protein folding
.
A third approach that structural biologists take to understanding structure is bioinformatics
to look for patterns among the diverse sequence
s that give rise to particular shapes. Researchers often can deduce aspects of the structure of integral membrane protein
s based on the membrane topology
predicted by hydrophobicity analysis. See protein structure prediction
.
In the past few years it has become possible for highly accurate physical molecular model
s to complement the in silico study of biological structures.
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
, biochemistry
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
, and biophysics
Biophysics
Biophysics is an interdisciplinary science that uses the methods of physical science to study biological systems. Studies included under the branches of biophysics span all levels of biological organization, from the molecular scale to whole organisms and ecosystems...
concerned with the molecular structure of biological macromolecule
Macromolecule
A macromolecule is a very large molecule commonly created by some form of polymerization. In biochemistry, the term is applied to the four conventional biopolymers , as well as non-polymeric molecules with large molecular mass such as macrocycles...
s, especially protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s and nucleic acid
Nucleic acid
Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...
s, how they acquire the structures they have, and how alterations in their structures affect their function. This subject is of great interest to biologists because macromolecules carry out most of the functions of cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
, and because it is only by coiling into specific three-dimensional shapes that they are able to perform these functions. This architecture, the "tertiary structure
Tertiary structure
In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...
" of molecules, depends in a complicated way on the molecules' basic composition, or "primary structure
Primary structure
The primary structure of peptides and proteins refers to the linear sequence of its amino acid structural units. The term "primary structure" was first coined by Linderstrøm-Lang in 1951...
s."
Biomolecule
A biomolecule is any molecule that is produced by a living organism, including large polymeric molecules such as proteins, polysaccharides, lipids, and nucleic acids as well as small molecules such as primary metabolites, secondary metabolites, and natural products...
s are too small to see in detail even with the most advanced light microscope
Microscope
A microscope is an instrument used to see objects that are too small for the naked eye. The science of investigating small objects using such an instrument is called microscopy...
s. The methods that structural biologists use to determine their structures generally involve measurements on vast numbers of identical molecules at the same time. These methods include:
- Macromolecular crystallography,
- NMR,
- EPRElectron paramagnetic resonanceElectron paramagnetic resonance or electron spin resonance spectroscopyis a technique for studying chemical species that have one or more unpaired electrons, such as organic and inorganic free radicals or inorganic complexes possessing a transition metal ion...
, - Cryo-electron microscopyCryo-electron microscopyCryo-electron microscopy , or electron cryomicroscopy, is a form of transmission electron microscopy where the sample is studied at cryogenic temperatures...
(cryo-EM) - Multiangle light scatteringMultiangle light scatteringMultiangle light scattering is a technique for determining, independently, the absolute molar mass and the average size of particles in solution, by detecting how they scatter light. Collimated light from a laser source is most often used, in which case the technique was referred to as multiangle...
, - Small angle scattering,
- Ultra fast laser spectroscopyUltra fast laser spectroscopyUltra-fast laser spectroscopy is the study of molecules on extremely short time scales after their excitation with a pulsed laser. This method is used extensively to examine the energy states and electron dynamics of any molecule whose reaction to light is of interest...
, and - Dual Polarisation InterferometryDual Polarisation InterferometryDual polarization interferometry is an analytical technique that can probe molecular scale layers adsorbed to the surface of a waveguide by using the evanescent wave of a laser beam confined to the waveguide...
and circular dichroismCircular dichroismCircular dichroism refers to the differential absorption of left and right circularly polarized light. This phenomenon was discovered by Jean-Baptiste Biot, Augustin Fresnel, and Aimé Cotton in the first half of the 19th century. It is exhibited in the absorption bands of optically active chiral...
.
Most often researchers use them to study the static "native state
Native state
In biochemistry, the native state of a protein is its operative or functional form. While all protein molecules begin as simple unbranched chains of amino acids, once completed they assume highly specific three-dimensional shapes; that ultimate shape, known as tertiary structure, is the folded...
s" of macromolecules. But variations on these methods are also used to watch nascent or denatured
Denaturation (biochemistry)
Denaturation is a process in which proteins or nucleic acids lose their tertiary structure and secondary structure by application of some external stress or compound, such as a strong acid or base, a concentrated inorganic salt, an organic solvent , or heat...
molecules assume or reassume their native states. See protein folding
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
.
A third approach that structural biologists take to understanding structure is bioinformatics
Bioinformatics
Bioinformatics is the application of computer science and information technology to the field of biology and medicine. Bioinformatics deals with algorithms, databases and information systems, web technologies, artificial intelligence and soft computing, information and computation theory, software...
to look for patterns among the diverse sequence
DNA sequence
The sequence or primary structure of a nucleic acid is the composition of atoms that make up the nucleic acid and the chemical bonds that bond those atoms. Because nucleic acids, such as DNA and RNA, are unbranched polymers, this specification is equivalent to specifying the sequence of...
s that give rise to particular shapes. Researchers often can deduce aspects of the structure of integral membrane protein
Integral membrane protein
An integral membrane protein is a protein molecule that is permanently attached to the biological membrane. Proteins that cross the membrane are surrounded by "annular" lipids, which are defined as lipids that are in direct contact with a membrane protein...
s based on the membrane topology
Membrane topology
In biochemistry, the membrane topology of an transmembrane protein describes which portions of the amino-acid sequence of the protein lie within the plane of the surrounding lipid bilayer and which portions protrude into the watery environment on either side...
predicted by hydrophobicity analysis. See protein structure prediction
Protein structure prediction
Protein structure prediction is the prediction of the three-dimensional structure of a protein from its amino acid sequence — that is, the prediction of its secondary, tertiary, and quaternary structure from its primary structure. Structure prediction is fundamentally different from the inverse...
.
In the past few years it has become possible for highly accurate physical molecular model
Molecular model
A molecular model, in this article, is a physical model that represents molecules and their processes. The creation of mathematical models of molecular properties and behaviour is molecular modelling, and their graphical depiction is molecular graphics, but these topics are closely linked and each...
s to complement the in silico study of biological structures.
See also
- Primary structurePrimary structureThe primary structure of peptides and proteins refers to the linear sequence of its amino acid structural units. The term "primary structure" was first coined by Linderstrøm-Lang in 1951...
- Secondary structureSecondary structureIn biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
- Tertiary structureTertiary structureIn biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...
- Quaternary structureQuaternary structureIn biochemistry, quaternary structure is the arrangement of multiple folded protein or coiling protein molecules in a multi-subunit complex.-Description and examples:...
- Structural domain
- Structural motifStructural motifIn a chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a supersecondary structure, which appears also in a variety of other molecules...
- Protein subunitProtein subunitIn structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein. Many naturally occurring proteins and enzymes are multimeric...
- Molecular modelMolecular modelA molecular model, in this article, is a physical model that represents molecules and their processes. The creation of mathematical models of molecular properties and behaviour is molecular modelling, and their graphical depiction is molecular graphics, but these topics are closely linked and each...
- CooperativityCooperativityCooperativity is a phenomenon displayed by enzymes or receptors that have multiple binding sites where the affinity of the binding sites for a ligand is increased, positive cooperativity, or decreased, negative cooperativity, upon the binding of a ligand to a binding site...
- ChaperoninChaperoninChaperonins are proteins that fold and unfold other proteins. Newly made proteins usually must fold from a linear chain of amino acids into a three-dimensional form. Chaperonins belong to a large class of molecules that assist protein folding, called molecular chaperones...
- Structural genomicsStructural genomicsStructural genomics seeks to describe the 3-dimensional structure of every protein encoded by a given genome. This genome-based approach allows for a high-throughput method of structure determination by a combination of experimental and modeling approaches...
- StereochemistryStereochemistryStereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms within molecules. An important branch of stereochemistry is the study of chiral molecules....
- Resolution (electron density)Resolution (electron density)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...
- ProteopediaProteopediaProteopedia is a wiki, 3D encyclopedia of proteins and other molecules..The site contains a page for every entry in the Protein Data Bank , as well as pages that are more descriptive of protein structures in general such as acetylcholinesterase, hemoglobin, and the photosystem II with a Jmol view...
The collaborative, 3D encyclopedia of proteins and other molecules.
External links
- Nature: Structural & Molecular Biology magazine website
- Structural Biology - The Virtual Library of Biochemistry and Cell Biology