Genetic Encoding of a Photocaged Histidine for Light‐Control of Protein Activity

Cheung, Jenny W.; Kinney, William D; Wesalo, Joshua S.; Reed, Megan R.; Nicholson, Eve M; Deiters, Alexander; Cropp, Ashton

doi:10.1002/cbic.202200721

Cited by 10 publications

(6 citation statements)

References 35 publications

(59 reference statements)

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“…More recently, with the aid of electrostatic surface potential calculations, a pyridine analogue of 1-pHis ( 39 , 1-pHis- m2 , Figure A) and a pyrazole analogue of 3-pHis ( 43 , 3-pHis- m4 , Figure A) were chosen as mimics, synthesized, and used successfully to create isomer selective antibodies . Encoding chemically protected forms of these analogues (to increase bioavailability) may be feasible given the plasticity of the pyrrolysine tRNA-RS/tRNA CUA pairs for encoding histidine analogues (e.g., methyl-histidine), − as well as recent discoveries of natural histidine RS/tRNA pairs that are orthogonal in E. coli …”

Section: Outlook On the Future Of Gce Technologies For “Less Studied”...mentioning

confidence: 99%

Genetic Encoding of Phosphorylated Amino Acids into Proteins

Allen,

Karplus,

Mehl

et al. 2024

Chem. Rev.

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Reversible phosphorylation is a fundamental mechanism for controlling protein function. Despite the critical roles phosphorylated proteins play in physiology and disease, our ability to study individual phospho-proteoforms has been hindered by a lack of versatile methods to efficiently generate homogeneous proteins with site-specific phosphoamino acids or with functional mimics that are resistant to phosphatases. Genetic code expansion (GCE) is emerging as a transformative approach to tackle this challenge, allowing direct incorporation of phosphoamino acids into proteins during translation in response to amber stop codons. This genetic programming of phospho-protein synthesis eliminates the reliance on kinase-based or chemical semisynthesis approaches, making it broadly applicable to diverse phospho-proteoforms. In this comprehensive review, we provide a brief introduction to GCE and trace the development of existing GCE technologies for installing phosphoserine, phosphothreonine, phosphotyrosine, and their mimics, discussing both their advantages as well as their limitations. While some of the technologies are still early in their development, others are already robust enough to greatly expand the range of biologically relevant questions that can be addressed. We highlight new discoveries enabled by these GCE approaches, provide practical considerations for the application of technologies by non-GCE experts, and also identify avenues ripe for further development.

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Section: Outlook On the Future Of Gce Technologies For “Less Studied”...mentioning

confidence: 99%

Genetic Encoding of Phosphorylated Amino Acids into Proteins

Allen,

Karplus,

Mehl

et al. 2024

Chem. Rev.

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“…213 ncAA 40, His carrying an ortho-nitrobenzyl group, was incorporated into proteins using a variant of MbPylRS. 214 This ncAA was incorporated into the chromophore of GFP, leading to an increase in fluorescence intensity upon UV irradiation. It was also successfully introduced into the essential His residue of type I chloramphenicol acetyltransferase, resulting in the enzyme's activation by UV light.…”

Section: Chemicalmentioning

confidence: 99%

“…Its compact size is advantageous, as it facilitates the identification of engineered aaRSs capable of incorporating ncAAs that contain the nitrobenzyl group. Considering these advantages, ncAAs containing the nitrobenzyl group, derived from Tyr, − Lys, ,− Cys, − Ser, Asp, Glu, and His, have been incorporated into proteins using GCE technology to regulate protein functions. Recent advances have led to the development of many derivatives with improved stability and photoreactivity, thereby overcoming the limitations of the nitrobenzyl group. ,, …”

Section: Controlling Protein Functions Using Caged Ncaasmentioning

confidence: 99%

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Cellular and Biophysical Applications of Genetic Code Expansion

Yi,

Lee,

Seo

et al. 2024

Chem. Rev.

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Despite their diverse functions, proteins are inherently constructed from a limited set of building blocks. These compositional constraints pose significant challenges to protein research and its practical applications. Strategically manipulating the cellular protein synthesis system to incorporate novel building blocks has emerged as a critical approach for overcoming these constraints in protein research and application. In the past two decades, the field of genetic code expansion (GCE) has achieved significant advancements, enabling the integration of numerous novel functionalities into proteins across a variety of organisms. This technological evolution has paved the way for the extensive application of genetic code expansion across multiple domains, including protein imaging, the introduction of probes for protein research, analysis of protein−protein interactions, spatiotemporal control of protein function, exploration of proteome changes induced by external stimuli, and the synthesis of proteins endowed with novel functions. In this comprehensive Review, we aim to provide an overview of cellular and biophysical applications that have employed GCE technology over the past two decades.

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“…NcAA can be incorporated into proteins by genetic code expansion technology through an orthogonal aminoacyl-tRNA synthetase (aaRS)/tRNA CUA pair (Manandhar et al, 2021). Several photocontrolled ncAA have been genetically encoded in Escherichia coli and mammalian cells, including analogs of tyrosine, lysine, cysteine, serine and histidine (Wu et al, 2004;Deiters et al, 2006;Lemke et al, 2007;Gautier et al, 2010;Arbely et al, 2012;Nguyen et al, 2014;Hauf et al, 2017;Luo et al, 2017;Baumann et al, 2019;Cheung et al, 2023). We choose to photocage tyrosines in the form of ortho-nitrobenzyl-tyrosine (NBY) for two reasons.…”

Section: Introductionmentioning

confidence: 99%

Regulation of IL-24/IL-20R2 complex formation using photocaged tyrosines and UV light

Pham

Zahradnı́k

Kolářová

et al. 2023

Front. Mol. Biosci.

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Human interleukin 24 (IL-24) is a multifunctional cytokine that represents an important target for autoimmune diseases and cancer. Since the biological functions of IL-24 depend on interactions with membrane receptors, on-demand regulation of the affinity between IL-24 and its cognate partners offers exciting possibilities in basic research and may have applications in therapy. As a proof-of-concept, we developed a strategy based on recombinant soluble protein variants and genetic code expansion technology to photocontrol the binding between IL-24 and one of its receptors, IL-20R2. Screening of non-canonical ortho-nitrobenzyl-tyrosine (NBY) residues introduced at several positions in both partners was done by a combination of biophysical and cell signaling assays. We identified one position for installing NBY, tyrosine70 of IL-20R2, which results in clear impairment of heterocomplex assembly in the dark. Irradiation with 365-nm light leads to decaging and reconstitutes the native tyrosine of the receptor that can then associate with IL-24. Photocaged IL-20R2 may be useful for the spatiotemporal control of the JAK/STAT phosphorylation cascade.

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Genetic Encoding of a Photocaged Histidine for Light‐Control of Protein Activity

Cited by 10 publications

References 35 publications

Genetic Encoding of Phosphorylated Amino Acids into Proteins

Genetic Encoding of Phosphorylated Amino Acids into Proteins

Cellular and Biophysical Applications of Genetic Code Expansion

Regulation of IL-24/IL-20R2 complex formation using photocaged tyrosines and UV light

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