In
biochemistry
Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, a ...
, a conformational change is a change in the shape of a
macromolecule
A macromolecule is a "molecule of high relative molecular mass, the structure of which essentially comprises the multiple repetition of units derived, actually or conceptually, from molecules of low relative molecular mass." Polymers are physi ...
, often induced by environmental factors.
A macromolecule is usually flexible and dynamic. Its shape can change in response to changes in its environment or other factors; each possible shape is called a conformation, and a transition between them is called a ''conformational change''. Factors that may induce such changes include temperature,
pH,
voltage
Voltage, also known as (electrical) potential difference, electric pressure, or electric tension, is the difference in electric potential between two points. In a Electrostatics, static electric field, it corresponds to the Work (electrical), ...
,
light
Light, visible light, or visible radiation is electromagnetic radiation that can be visual perception, perceived by the human eye. Visible light spans the visible spectrum and is usually defined as having wavelengths in the range of 400– ...
in
chromophore
A chromophore is the part of a molecule responsible for its color. The word is derived .
The color that is seen by our eyes is that of the light not Absorption (electromagnetic radiation), absorbed by the reflecting object within a certain wavele ...
s,
concentration
In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'', ...
of
ions,
phosphorylation
In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols:
:
This equation can be writ ...
, or the binding of a
ligand
In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...
. Transitions between these states occur on a variety of length scales (tenths of Å to nm) and time scales (ns to s),
and have been linked to functionally relevant phenomena such as
allosteric signaling and
enzyme catalysis.
Laboratory analysis
Many biophysical techniques such as
crystallography
Crystallography is the branch of science devoted to the study of molecular and crystalline structure and properties. The word ''crystallography'' is derived from the Ancient Greek word (; "clear ice, rock-crystal"), and (; "to write"). In J ...
,
NMR
Nuclear magnetic resonance (NMR) is a physical phenomenon in which atomic nucleus, nuclei in a strong constant magnetic field are disturbed by a weak oscillating magnetic field (in the near and far field, near field) and respond by producing ...
,
electron paramagnetic resonance (EPR) using
spin label techniques,
circular dichroism (CD),
hydrogen exchange, and
FRET can be used to study macromolecular conformational change.
Dual-polarization interferometry is a benchtop technique capable of providing information about conformational changes in biomolecules.
A specific nonlinear optical technique called second-harmonic generation (SHG) has been recently applied to the study of conformational change in proteins. In this method, a second-harmonic-active probe is placed at a site that undergoes motion in the protein by mutagenesis or non-site-specific attachment, and the protein is adsorbed or specifically immobilized to a surface. A change in protein conformation produces a change in the net orientation of the dye relative to the surface plane and therefore the intensity of the second harmonic beam. In a protein sample with a well-defined orientation, the tilt angle of the probe can be quantitatively determined, in real space and real time. Second-harmonic-active unnatural amino acids can also be used as probes.
Another method applies
electro-switchable biosurfaces where proteins are placed on top of short DNA molecules which are then dragged through a buffer solution by application of alternating electrical potentials. By measuring their speed which ultimately depends on their hydrodynamic friction, conformational changes can be visualized.
"Nanoantennas" made out of DNA – a novel type of nano-scale
optical antenna – can be attached to proteins and produce a signal via
fluorescence
Fluorescence is one of two kinds of photoluminescence, the emission of light by a substance that has absorbed light or other electromagnetic radiation. When exposed to ultraviolet radiation, many substances will glow (fluoresce) with colore ...
for their distinct conformational changes.
Computational analysis
X-ray crystallography
X-ray crystallography is the experimental science of determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to Diffraction, diffract in specific directions. By measuring th ...
can provide information about changes in conformation at the atomic level, but the expense and difficulty of such experiments make computational methods an attractive alternative. Normal
mode analysis with elastic network models, such as the
Gaussian network model, can be used to probe
molecular dynamics
Molecular dynamics (MD) is a computer simulation method for analyzing the Motion (physics), physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a fixed period of time, giving a view of the dynamics ( ...
trajectories as well as known structures. ProDy is a popular tool for such analysis.
Examples
Conformational changes are important for:
*
ABC transporters
* catalysis
* cellular locomotion and
motor proteins
* formation of
protein complexes
A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multidomain enzymes, in which multiple catalytic domains are found in a single polypeptide chain.
Protein c ...
*
ion channel
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...
s
*
mechanoreceptor
A mechanoreceptor, also called mechanoceptor, is a sensory receptor that responds to mechanical pressure or distortion. Mechanoreceptors are located on sensory neurons that convert mechanical pressure into action potential, electrical signals tha ...
s and
mechanotransduction
* regulatory activity
* transport of metabolites across
cell membrane
The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
s
See also
*
Database of protein conformational diversity
*
Protein dynamics
*
The Database of Macromolecular Motions (molmovdb)
References
External links
Frauenfelder, H. New looks at protein motions Nature 338, 623 - 624 (20 April 1989)
Sensing with electro-switchable biosurfaces{{DEFAULTSORT:Conformational Change
Microbiology techniques