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Review
. 2023 Jan 26;3(2):344-357.
doi: 10.1021/jacsau.2c00654. eCollection 2023 Feb 27.

Strategies for Conditional Regulation of Proteins

Karthik Nadendla  1 , Grant G Simpson  1 , Julie Becher  1 , Toby Journeaux  1 , Mar Cabeza-Cabrerizo  1 , Gonçalo J L Bernardes  1   2
Affiliations
Review

Strategies for Conditional Regulation of Proteins

Karthik Nadendla et al. JACS Au. .

Abstract

Design of the next-generation of therapeutics, biosensors, and molecular tools for basic research requires that we bring protein activity under control. Each protein has unique properties, and therefore, it is critical to tailor the current techniques to develop new regulatory methods and regulate new proteins of interest (POIs). This perspective gives an overview of the widely used stimuli and synthetic and natural methods for conditional regulation of proteins.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Outline of the modes of regulation and types of stimuli used for conditional regulation of proteins.
Figure 2
Figure 2
Regulation of protein activity through noncovalent interactions. (a) Small or macromolecules directly influence the activity of POI. (b) Different bivalent ligands designed to create neo interactions between two different POIs. (c) Split inteins. (d) Protein complementation.
Figure 3
Figure 3
Protein regulation through (a) domain swapping, (b) histidine switches, and (c) azobenzenes.
Figure 4
Figure 4
Protein regulation via (a) proteolytic action, (b) caging/decaging chemistry, and (c) tethered pharmacology.
Figure 5
Figure 5
Protein regulation by compartmentalization.
See this image and copyright information in PMC

References

    1. Ponomarenko E. A.; Poverennaya E. V.; Ilgisonis E. V.; Pyatnitskiy M. A.; Kopylov A. T.; Zgoda V. G.; Lisitsa A. V.; Archakov A. I. The Size of the Human Proteome: The Width and Depth. Int. J. Anal. Chem. 2016, 2016, 1–6. 10.1155/2016/7436849. - DOI - PMC - PubMed
    1. Omenn G. S.; Lane L.; Overall C. M.; Cristea I. M.; Corrales F. J.; Lindskog C.; Paik Y.-K.; Van Eyk J. E.; Liu S.; Pennington S. R.; others; et al. Research on the Human Proteome Reaches a Major Milestone:> 90% of Predicted Human Proteins Now Credibly Detected, According to the HUPO Human Proteome Project. J. Proteome Res. 2020, 19 (12), 4735–4746. 10.1021/acs.jproteome.0c00485. - DOI - PMC - PubMed
    1. Lodish H. F.; Berk A.; Kaiser C. A.; Krieger M.; Bretscher A.; Ploegh H.; Amon A.; Martin K. C.. Molecular Cell Biology, 8th ed.; W.H. Freeman and Company: New York, 2016.
    1. Thomas L. W.; Esposito C.; Morgan R. E.; Price S.; Young J.; Williams S. P.; Maddalena L. A.; McDermott U.; Ashcroft M. Genome-Wide CRISPR/Cas9 Deletion Screen Defines Mitochondrial Gene Essentiality and Identifies Routes for Tumour Cell Viability in Hypoxia. Commun. Biol. 2021, 4 (1), 615. 10.1038/s42003-021-02098-x. - DOI - PMC - PubMed
    1. Nadendla K.; Sarode B.; Friedman S. H.. Chemical Modification of Proteins with Photocleavable Groups. In Methods in Enzymology; Elsevier, 2019; Vol. 624, pp 113–128. 10.1016/bs.mie.2019.04.008. - DOI - PMC - PubMed