Conformational change

In biochemistry, a conformational change is a change in the shape of a macromolecule, 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, light in chromophores, concentration of ions, phosphorylation, or the binding of a ligand. 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^[1] and enzyme catalysis.^[2]

Laboratory analysis

Many biophysical techniques such as

A specific nonlinear optical technique called second-harmonic generation (SHG) has been recently applied to the study of conformational change in proteins.[4] 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.^{[citation needed]}

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.^{[citation needed]}

"Nanoantennas" made out of DNA – a novel type of nano-scale optical antenna – can be attached to proteins and produce a signal via fluorescence for their distinct conformational changes.^[5][6]

Computational analysis

X-ray crystallography 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.^[7] Normal mode analysis with elastic network models, such as the Gaussian network model, can be used to probe molecular dynamics trajectories as well as known structures.^[8][9] ProDy is a popular tool for such analysis.^[10]

Examples

Conformational changes are important for:

• ABC transporters ^[11]
• catalysis^[12]
• cellular locomotion and
  motor proteins^[13]
• formation of
  protein complexes^[14]
• ion channels^[15]
• mechanoreceptors and mechanotransduction^[16]
• regulatory activity ^[17]
• transport of metabolites across cell membranes ^[18][19]

See also

• Database of protein conformational diversity
• Protein dynamics
• The Database of Macromolecular Motions (molmovdb)

References