Protein Conformational Switches: From Nature to Design
- 11 June 2012
- journal article
- review article
- Published by Wiley in Chemistry – A European Journal
- Vol. 18 (26), 7984-7999
- https://doi.org/10.1002/chem.201200348
Abstract
Protein conformational switches alter their shape upon receiving an input signal, such as ligand binding, chemical modification, or change in environment. The apparent simplicity of this transformation—which can be carried out by a molecule as small as a thousand atoms or so—belies its critical importance to the life of the cell as well as its capacity for engineering by humans. In the realm of molecular switches, proteins are unique because they are capable of performing a variety of biological functions. Switchable proteins are therefore of high interest to the fields of biology, biotechnology, and medicine. These molecules are beginning to be exploited as the core machinery behind a new generation of biosensors, functionally regulated enzymes, and “smart” biomaterials that react to their surroundings. As inspirations for these designs, researchers continue to analyze existing examples of allosteric proteins. Recent years have also witnessed the development of new methodologies for introducing conformational change into proteins that previously had none. Herein we review examples of both natural and engineered protein switches in the context of four basic modes of conformational change: rigid‐body domain movement, limited structural rearrangement, global fold switching, and folding–unfolding. Our purpose is to highlight examples that can potentially serve as platforms for the design of custom switches. Accordingly, we focus on inducible conformational changes that are substantial enough to produce a functional response (e.g., in a second protein to which it is fused), yet are relatively simple, structurally well‐characterized, and amenable to protein engineering efforts.This publication has 180 references indexed in Scilit:
- Light Control of Plasma Membrane Recruitment Using the Phy–PIF SystemMethods in Enzymology, 2011
- Cytoskeletal protein kinases: titin and its relations in mechanosensingPflügers Archiv - European Journal of Physiology, 2011
- Converting a protein into a switch for biosensing and functional regulationProtein Science, 2010
- On the mechanism of protein fold-switching by a molecular sensorProteins-Structure Function and Bioinformatics, 2010
- Differential Regulation of Protrusion and Polarity by PI(3)K during Neutrophil Motility in Live ZebrafishDevelopmental Cell, 2010
- Understanding protein non-foldingBiochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2010
- N‐terminal strands of filamin Ig domains act as a conformational switch under biological forcesProteins-Structure Function and Bioinformatics, 2009
- Generation of new protein functions by nonhomologous combinations and rearrangements of domains and modulesCurrent Opinion in Biotechnology, 2009
- Effect of Interdomain Linker Length on an Antagonistic Folding–Unfolding Equilibrium between Two Protein DomainsJournal of Molecular Biology, 2009
- Cell adhesion receptors in mechanotransductionCurrent Opinion in Cell Biology, 2008