Conformational change

{{Short description|Change in the shape of a macromolecule, often induced by environmental factors}}

Image:Kinesin_walking.gif. Kinesin walking on a microtubule is a molecular biological machine using protein domain dynamics on nanoscales]]{{Main|Protein dynamics}}

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{{Cite book | vauthors = Bu Z, Callaway DJ | title = Protein Structure and Diseases | chapter = Proteins move! Protein dynamics and long-range allostery in cell signaling | journal = Advances in Protein Chemistry and Structural Biology | volume = 83 | pages = 163–221 | year = 2011 | pmid = 21570668 | doi = 10.1016/B978-0-12-381262-9.00005-7 | isbn = 9780123812629 }} and enzyme catalysis.

{{cite journal | vauthors = Fraser JS, Clarkson MW, Degnan SC, Erion R, Kern D, Alber T | title = Hidden alternative structures of proline isomerase essential for catalysis | journal = Nature | volume = 462 | issue = 7273 | pages = 669–73 | date = December 2009 | pmid = 19956261 | pmc = 2805857 | doi = 10.1038/nature08615 | bibcode = 2009Natur.462..669F }}

Laboratory analysis

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-polarization interferometry is a benchtop technique capable of providing information about conformational changes in biomolecules.{{Cite journal| vauthors = Freeman NJ, Peel LL, Swann MJ, Cross GH, Reeves A, Brand S, Lu JR |date=2004-06-19|title=Real time, high resolution studies of protein adsorption and structure at the solid–liquid interface using dual polarization interferometry|url=https://iopscience.iop.org/article/10.1088/0953-8984/16/26/023|journal=Journal of Physics: Condensed Matter|volume=16|issue=26|pages=S2493–S2496|doi=10.1088/0953-8984/16/26/023|bibcode=2004JPCM...16S2493F |s2cid=250737643 |issn=0953-8984|url-access=subscription}}

A specific nonlinear optical technique called second-harmonic generation (SHG) has been recently applied to the study of conformational change in proteins.{{cite journal | vauthors = Salafsky JS, Cohen B | title = A second-harmonic-active unnatural amino acid as a structural probe of biomolecules on surfaces | journal = The Journal of Physical Chemistry B | volume = 112 | issue = 47 | pages = 15103–7 | date = November 2008 | pmid = 18928314 | doi = 10.1021/jp803703m }} 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|date=July 2019}}

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|date=January 2022}}

"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.{{cite news |title=Chemists use DNA to build the world's tiniest antenna |url=https://phys.org/news/2022-01-chemists-dna-world-tiniest-antenna.html |access-date=19 January 2022 |work=University of Montreal |language=en}}{{cite journal |last1=Harroun |first1=Scott G. |last2=Lauzon |first2=Dominic |last3=Ebert |first3=Maximilian C. C. J. C. |last4=Desrosiers |first4=Arnaud |last5=Wang |first5=Xiaomeng |last6=Vallée-Bélisle |first6=Alexis |title=Monitoring protein conformational changes using fluorescent nanoantennas |journal=Nature Methods |date=January 2022 |volume=19 |issue=1 |pages=71–80 |doi=10.1038/s41592-021-01355-5 |pmid=34969985 |s2cid=245593311 |language=en |issn=1548-7105|doi-access=free }}

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.{{cite journal | vauthors = Kim Y, Bigelow L, Borovilos M, Dementieva I, Duggan E, Eschenfeldt W, Hatzos C, Joachimiak G, Li H, Maltseva N, Mulligan R, Quartey P, Sather A, Stols L, Volkart L, Wu R, Zhou M, Joachimiak A | display-authors = 6 | title = Chapter 3. High-throughput protein purification for x-ray crystallography and NMR | journal = Advances in Protein Chemistry and Structural Biology | volume = 75 | pages = 85–105 | date = 2008-01-01 | pmid = 20731990 | doi = 10.1016/S0065-3233(07)75003-9 | pmc = 3366499 }} 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.{{cite journal | vauthors = Tang QY, Kaneko K | title = Long-range correlation in protein dynamics: Confirmation by structural data and normal mode analysis | journal = PLOS Computational Biology | volume = 16 | issue = 2 | pages = e1007670 | date = February 2020 | pmid = 32053592 | pmc = 7043781 | doi = 10.1371/journal.pcbi.1007670 | bibcode = 2020PLSCB..16E7670T | doi-access = free }}{{cite journal | vauthors = Zheng W, Doniach S | title = A comparative study of motor-protein motions by using a simple elastic-network model | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 23 | pages = 13253–8 | date = November 2003 | pmid = 14585932 | doi = 10.1073/pnas.2235686100 | pmc = 263771 | bibcode = 2003PNAS..10013253Z | doi-access = free }} ProDy is a popular tool for such analysis.{{cite journal | vauthors = Bakan A, Meireles LM, Bahar I | title = ProDy: protein dynamics inferred from theory and experiments | journal = Bioinformatics | volume = 27 | issue = 11 | pages = 1575–7 | date = June 2011 | pmid = 21471012 | doi = 10.1093/bioinformatics/btr168 | pmc = 3102222 }}

Examples

Conformational changes are important for:

ABC transporters {{cite book | veditors = Ponte-Sucre A | year=2009 |title=ABC Transporters in Microorganisms | publisher=Caister Academic | isbn= 978-1-904455-49-3}}
catalysis{{cite journal | vauthors = Kamerlin SC, Warshel A | title = At the dawn of the 21st century: Is dynamics the missing link for understanding enzyme catalysis? | journal = Proteins | volume = 78 | issue = 6 | pages = 1339–75 | date = May 2010 | pmid = 20099310 | pmc = 2841229 | doi = 10.1002/prot.22654 }}
cellular locomotion and motor proteins{{Cite book|title=Mechanics of motor proteins and the cytoskeleton| vauthors = Howard J |date=2001|publisher=Sinauer Associates|isbn=9780878933334|edition= 1st|location=Sunderland,MA}}
formation of protein complexes{{cite journal | vauthors = Callaway DJ, Matsui T, Weiss T, Stingaciu LR, Stanley CB, Heller WT, Bu Z | title = Controllable Activation of Nanoscale Dynamics in a Disordered Protein Alters Binding Kinetics | journal = Journal of Molecular Biology | volume = 429 | issue = 7 | pages = 987–998 | date = April 2017 | pmid = 28285124 | pmc = 5399307 | doi = 10.1016/j.jmb.2017.03.003 }}
ion channels{{cite book | author-link1=Bertil Hille | vauthors = Hille B | title = Ion Channels of Excitable Membranes | edition = 3rd | publisher = Sinauer Associates, Inc. | location = Sunderland, Mass | year = 2001 | orig-year = 1984 | pages = 5 | isbn = 978-0-87893-321-1 }}
mechanoreceptors and mechanotransduction{{cite journal | vauthors = Nicholl ID, Matsui T, Weiss TM, Stanley CB, Heller WT, Martel A, Farago B, Callaway DJ, Bu Z | display-authors = 6 | title = α-Catenin Structure and Nanoscale Dynamics in Solution and in Complex with F-Actin | journal = Biophysical Journal | volume = 115 | issue = 4 | pages = 642–654 | date = August 2018 | pmid = 30037495 | pmc = 6104293 | doi = 10.1016/j.bpj.2018.07.005 | bibcode = 2018BpJ...115..642N | hdl = 2436/621755 }}
regulatory activity {{Cite book|title=Biochemistry| vauthors = Donald V |date=2011|publisher=John Wiley & Sons|others=Voet, Judith G.|isbn=9780470570951|edition= 4th|location=Hoboken, NJ|oclc=690489261}}
transport of metabolites across cell membranes [http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellMembranes.html Kimball's Biology pages] {{webarchive|url=https://web.archive.org/web/20090125224255/http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellMembranes.html |date=2009-01-25 }}, Cell Membranes{{cite book | vauthors = Singleton P |title=Bacteria in Biology, Biotechnology and Medicine |edition=5th |isbn=978-0-471-98880-9 |year=1999 |publisher=Wiley |location=New York}}

References

External links

[http://www.nature.com/nature/journal/v338/n6217/abs/338623a0.html Frauenfelder, H. New looks at protein motions Nature 338, 623 - 624 (20 April 1989)].
[https://link.springer.com/article/10.1007%2Fs12566-012-0030-0 Sensing with electro-switchable biosurfaces]

Category:Microbiology techniques