Conformational change

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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. It can change its shape 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, ion concentration, 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[edit]

Many biophysical techniques such as crystallography, NMR, electron paramagnetic resonance (EPR) using spin label techniques, circular dichroism (CD), hydrogen exchange, and FRET can be used to study macromolecular conformational change. Dual polarisation interferometry is a benchtop technique capable of measuring conformational changes in biomolecules in real time at very high resolution.

A specific nonlinear optical technique called second-harmonic generation (SHG) has been recently applied to the study of conformational change in proteins.[3] 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.


Conformational changes are important for:

See also[edit]

External links[edit]


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  2. ^ Fraser JS, Clarkson MW, Degnan SC, Erion R, Kern D, Alber T (Dec 2009). "Hidden alternative structures of proline isomerase essential for catalysis". Nature. 462 (7273): 669–673. Bibcode:2009Natur.462..669F. doi:10.1038/nature08615. PMC 2805857. PMID 19956261.
  3. ^ Salafsky, Joshua S.; Cohen, Bruce (2008). "A Second-Harmonic-Active Unnatural Amino Acid as a Structural Probe of Biomolecules on Surfaces". Journal of Physical Chemistry. 112 (47): 15103–15107. doi:10.1021/jp803703m. PMID 18928314.
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  5. ^ Kamerlin SC, Warshel A (May 2010). "At the dawn of the 21st century: Is dynamics the missing link for understanding enzyme catalysis?". Proteins. 78 (6): 1339–75. doi:10.1002/prot.22654. PMC 2841229. PMID 20099310.
  6. ^ Howard, Jonathan (2001). Mechanics of motor proteins and the cytoskeleton (1st ed.). Sunderland,MA: Sinauer Associates. ISBN 9780878933334.
  7. ^ Callaway DJ, Matsui T, Weiss T, Stingaciu LR, Stanley CB, Heller WT, Bu Z (Apr 2017). "Controllable Activation of Nanoscale Dynamics in a Disordered Protein Alters Binding Kinetics". Journal of Molecular Biology. 429 (7): 987–998. doi:10.1016/j.jmb.2017.03.003. PMC 5399307. PMID 28285124.
  8. ^ Hille B (2001) [1984]. Ion Channels of Excitable Membranes (3rd ed.). Sunderland, Mass: Sinauer Associates, Inc. p. 5. ISBN 978-0-87893-321-1.
  9. ^ Nicholl ID, Matsui T, Weiss TM, Stanley CB, Heller WT, Martel A, Farago B, Callaway DJ, Bu Z (Aug 21, 2018). "Alpha-catenin structure and nanoscale dynamics in solution and in complex with F-actin". Biophysical Journal. 115 (4): 642–654. doi:10.1016/j.bpj.2018.07.005. hdl:2436/621755. PMC 6104293. PMID 30037495.
  10. ^ Donald, Voet (2011). Biochemistry. Voet, Judith G. (4th ed.). Hoboken, NJ: John Wiley & Sons. ISBN 9780470570951. OCLC 690489261.
  11. ^ Kimball's Biology pages Archived 2009-01-25 at the Wayback Machine, Cell Membranes
  12. ^ Singleton P (1999). Bacteria in Biology, Biotechnology and Medicine (5th ed.). New York: Wiley. ISBN 978-0-471-98880-9.