Design of Light-Controlled Protein Conformations and Functions

  • Ryan S. Ritterson
  • Daniel Hoersch
  • Kyle A. Barlow
  • Tanja KortemmeEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1414)


In recent years, interest in controlling protein function with light has increased. Light offers a number of unique advantages over other methods, including spatial and temporal control and high selectivity. Here, we describe a general protocol for engineering a protein to be controllable with light via reaction with an exogenously introduced photoisomerizable small molecule and illustrate our protocol with two examples from the literature: the engineering of the calcium affinity of the cell–cell adhesion protein cadherin, which is an example of a protein that switches from a native to a disrupted state (Ritterson et al. J Am Chem Soc (2013) 135:12516–12519), and the engineering of the opening and closing of the chaperonin Mm-cpn, an example of a switch between two functional states (Hoersch et al.: Nat Nanotechn (2013) 8:928–932). This protocol guides the user from considering which proteins may be most amenable to this type of engineering, to considerations of how and where to make the desired changes, to the assays required to test for functionality.

Key words

Photoswitches Computational protein design Light-modulatable proteins Protein engineering 



Work on light-switchable protein functions in our group was supported by grants from the Program for Breakthrough Biomedical Research and the Sandler Family Foundation (to T. K.), the National Institutes of Health (PN2EY016525, PI Wah Chiu), the National Science Foundation (NSF CBET-1134127 to T.K.), and a Deutsche Forschungsgemeinschaft postdoctoral fellowship (HO 4429/2-1 to D.H.). We particularly thank A. Woolley (U Toronto) for the advice, discussions, and gifts of ABDM and BSBCA.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Ryan S. Ritterson
    • 1
  • Daniel Hoersch
    • 1
    • 2
  • Kyle A. Barlow
    • 3
  • Tanja Kortemme
    • 1
    Email author
  1. 1.California Institute for Quantitative Biomedical Research and Department of Bioengineering and Therapeutic SciencesUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Fachbereich PhysikFreie Universität BerlinBerlinGermany
  3. 3.Graduate Program in Bioinformatics, California Institute for Quantitative Biomedical Research, and Department of Bioengineering and Therapeutic SciencesUniversity of California, San FranciscoSan FranciscoUSA

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