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Biophysics  2021 

tRNA修饰酶TiaS蛋白结构与功能研究及其锌指的潜在应用
Research on the Structure and Function of tRNA-Modifying Enzyme TiaS and Potential Applications of Its Zinc Ribbon

DOI: 10.12677/BIPHY.2021.91002, PP. 10-21

Keywords: 锌指,tRNA修饰,TiaS蛋白,酶催化,核酸靶向
Zinc Ribbon
, tRNA Modification, TiaS Protein, Enzymatic Catalysis, Nucleic Acid Targeting

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Abstract:

含有锌指的TiaS (tRNAIle2 agmatidine synthetase)蛋白是来自古菌的酶,具有四个结构域,功能是利用ATP水解释放的能量在tRNAIle2反密码子CAU的简并碱基胞嘧啶Cyt34的2’碳原子上面加上胍基丁胺Agmatine修饰,从而让tRNAIle2成熟不识别AUG,而正确识别AUA密码子。单独TiaS蛋白,TiaS蛋白与tRNA复合物结构已经解析,酶催化修饰的分子机制获得了较深入解读。生化实验表明,TiaS蛋白N端三个结构域具有催化活性,TiaS为焦磷酸酶,可以水解ATP。并且TiaS蛋白的N端结构域可以起到激酶的作用,自磷酸化Thr18氨基酸残基。C端锌指距离酶核心较远,对于识别结合底物具有重要作用。本文总结TiaS蛋白研究进展。对于TiaS蛋白的深入研究,将为深入理解酶催化机制,为酶的工程改造,为锌指的工程改造开辟思路。包括锌指与CRISPR/Cas在内的靶向核酸元件在生命医药和研究领域有广泛应用,TiaS蛋白锌指结构新特性的研究也为基于锌指的靶向核酸组件设计打下基础。
Archaeal TiaS (tRNAIle2 agmatidine synthetase) protein is a zinc-ribbon containing four-domain tRNAIle2 modifying enzyme, which is able to hydrolyze ATP and modify the 2’carbon of the wobble position cytosine 34 with Agmatine (Agm). The modification is essential for tRNAIle2 maturation and thus for accurate deciphering of AUA codon. The enzyme core consisting of the N-terminal three domains is responsible for the catalytic activity. The C-terminal zinc ribbon domain (ZRD) is far away from the enzyme core, and plays important role in substrate tRNA recognition and discrimination. Further research of TiaS will provide significant insight into the mechanism of enzyme catalysis and pave ways for enzyme engineering. Zinc finger engineering and targetable nucleases (by using zinc fingers or CRISPR/Cas) engineering have wide applications ranging from research to medicine. New characteristics about zinc ribbon and zinc ribbon-nucleic acid interaction may help future designs of targetable proteins for applications in genetic modulation, genome manipulation or therapeutics research.

References

[1]  Cantara, W.A., Crain, P.F., Rozenski, J., McCloskey, J.A., Harris, K.A., Zhang, X., et al. (2011) The RNA Modification Database, RNAMDB: 2011 Update. Nucleic Acids Research, 39, D195-D201.
https://doi.org/10.1093/nar/gkq1028
[2]  Machnicka, M.A., Milanowska, K., Osman Oglou, O., Purta, E., Kurkowska, M., Olchowik, A., et al. (2013) MODOMICS: A Database of RNA Modification Pathways—2013 Update. Nucleic Acids Research, 41, D262-D267.
https://doi.org/10.1093/nar/gks1007
[3]  Marcus, J.O. and Bystro, A.S. (2005) Transfer RNA Modifications and Modifying Enzymes in Saccharomyces cerevisiae. In: Grosjean, H., Ed., Fine-Tuning of RNA Functions by Modification and Editing, Vol. 12, Springer, New York, 87-119.
https://doi.org/10.1007/b105814
[4]  Soma, A., Ikeuchi, Y., Kanemasa, S., Kobayashi, K., Ogasawara, N., Ote, T., et al. (2003) An RNA-Modifying Enzyme That Governs both the Codon and Amino Acid Specificities of Isoleucine tRNA. Molecular Cell, 12, 689-698.
https://doi.org/10.1016/S1097-2765(03)00346-0
[5]  Ikeuchi, Y., Soma, A., Ote, T., Kato, J., Sekine, Y. and Suzuki, T. (2005) Molecular Mechanism of Lysidine Synthesis That Determines tRNA Identity and Codon Recognition. Molecular Cell, 19, 235-246.
https://doi.org/10.1016/j.molcel.2005.06.007
[6]  Nakanishi, K., Fukai, S., Ikeuchi, Y., Soma, A., Sekine, Y., Suzuki, T., et al. (2005) Structural Basis for Lysidine Formation by ATP Pyrophosphatase Accompanied by a Lysine-Specific Loop and a tRNA-Recognition Domain. Proceedings of the National Academy of Sciences of the United States of America, 102, 7487-7492.
https://doi.org/10.1073/pnas.0501003102
[7]  Grosjean, H. and Bjork, G.R. (2004) Enzymatic Conversion of Cytidine to Lysidine in Anticodon of Bacterial Isoleucyl-tRNA—An Alternative Way of RNA Editing. Trends in Biochemical Sciences, 29, 165-168.
https://doi.org/10.1016/j.tibs.2004.02.009
[8]  Nakanishi, K., Bonnefond, L., Kimura, S., Suzuki, T., Ishitani, R. and Nureki, O. (2009) Structural Basis for Translational Fidelity Ensured by Transfer RNA Lysidine Synthetase. Nature, 461, 1144-1148.
https://doi.org/10.1038/nature08474
[9]  Kuratani, M., Yoshikawa, Y., Bessho, Y., Higashijima, K., Ishii, T., Shibata, R., et al. (2007) Structural Basis of the Initial Binding of tRNA(Ile) Lysidine Synthetase TilS with ATP and L-Lysine. Structure, 15, 1642-1653.
https://doi.org/10.1016/j.str.2007.09.020
[10]  Muramatsu, T., Nishikawa, K., Nemoto, F., Kuchino, Y., Nishimura, S., Miyazawa, T., et al. (1988) Codon and Amino-Acid Specificities of a Transfer RNA Are both Converted by a Single Post-Transcriptional Modification. Nature, 336, 179-181.
https://doi.org/10.1038/336179a0
[11]  Gupta, R. (1984) Halobacterium volcanii tRNAs. Identification of 41 tRNAs Covering All Amino Acids, and the Sequences of 33 Class I tRNAs. Journal of Biological Chemistry, 259, 9461-9471.
https://doi.org/10.1016/S0021-9258(17)42723-2
[12]  Mandal, D., Kohrer, C., Su, D., Russell, S.P., Krivos, K., Castleberry, C.M., et al. (2010) Agmatidine, a Modified Cytidine in the Anticodon of Archaeal tRNA(Ile), Base Pairs with Adenosine But Not with Guanosine. Proceedings of the National Academy of Sciences of the United States of America, 107, 2872-2877.
https://doi.org/10.1073/pnas.0914869107
[13]  Ikeuchi, Y., Kimura, S., Numata, T., Nakamura, D., Yokogawa, T., Ogata, T., et al. (2010) Agmatine-Conjugated Cytidine in a tRNA Anticodon Is Essential for AUA Decoding in Archaea. Nature Chemical Biology, 6, 277-282.
https://doi.org/10.1038/nchembio.323
[14]  Kohrer, C., Srinivasan, G., Mandal, D., Mallick, B., Ghosh, Z., Chakrabarti, J., et al. (2008) Identification and Characterization of a tRNA Decoding the Rare AUA Codon in Haloarcula marismortui. Rna, 14, 117-126.
https://doi.org/10.1261/rna.795508
[15]  Reis, D.J. and Regunathan, S. (2000) Is Agmatine a Novel Neurotransmitter in Brain? Trends in Pharmacological Sciences, 21, 187-193.
https://doi.org/10.1016/S0165-6147(00)01460-7
[16]  Halaris, A. and Plietz, J. (2007) Agmatine: Metabolic Pathway and Spectrum of Activity in Brain. CNS Drugs, 21, 885-900.
https://doi.org/10.2165/00023210-200721110-00002
[17]  Osawa, T., Kimura, S., Terasaka, N., Inanaga, H., Suzuki, T. and Numata, T. (2011) Structural Basis of tRNA Agmatinylation Essential for AUA Codon Decoding. Nature Structural & Molecular Biology, 18, 1275-1280.
https://doi.org/10.1038/nsmb.2144
[18]  Terasaka, N., Kimura, S., Osawa, T., Numata, T. and Suzuki, T. (2011) Biogenesis of 2-Agmatinylcytidine Catalyzed by the Dual Protein and RNA Kinase TiaS. Nature Structural & Molecular Biology, 18, 1268-1274.
https://doi.org/10.1038/nsmb.2121
[19]  Li, F., Dong, J., Hu, X., Gong, W., Li, J., Shen, J., et al. (2015) A Covalent Approach for Site-Specific RNA Labeling in Mammalian Cells. Angewandte Chemie International Edition in English, 54, 4597-4602.
https://doi.org/10.1002/anie.201410433
[20]  Dong, J., Li, F., Gao, F., Wei, J., Lin, Y., Zhang, Y., et al. (2018) Structure of tRNA-Modifying Enzyme TiaS and Motions of Its Substrate Binding Zinc Ribbon. Journal of Molecular Biology, 430, 4183-4194.
https://doi.org/10.1016/j.jmb.2018.08.015
[21]  Bauer, J.A., Pavlovic, J. and Bauerova-Hlinkova, V. (2019) Normal Mode Analysis as a Routine Part of a Structural Investigation. Molecules, 24, 3293.
https://doi.org/10.3390/molecules24183293
[22]  Eyal, E., Lum, G. and Bahar, I. (2015) The Anisotropic Network Model Web Server at 2015 (ANM 2.0). Bioinformatics, 31, 1487-1489.
https://doi.org/10.1093/bioinformatics/btu847
[23]  Lindahl, E., Azuara, C., Koehl, P. and Delarue, M. (2006) NOMAD-Ref: Visualization, Deformation and Refinement of Macromolecular Structures Based on All-Atom Normal Mode Analysis. Nucleic Acids Research, 34, W52-W56.
https://doi.org/10.1093/nar/gkl082
[24]  Laity, J.H., Lee, B.M. and Wright, P.E. (2001) Zinc Finger Proteins: New Insights into Structural and Functional Diversity. Current Opinion in Structural Biology, 11, 39-46.
https://doi.org/10.1016/S0959-440X(00)00167-6
[25]  Brown, R.S. (2005) Zinc Finger Proteins: Getting a Grip on RNA. Current Opinion in Structural Biology, 15, 94-98.
https://doi.org/10.1016/j.sbi.2005.01.006
[26]  Krishna, S.S., Majumdar, I. and Grishin, N.V. (2003) Structural Classification of Zinc Fingers: Survey and Summary. Nucleic Acids Research, 31, 532-550.
https://doi.org/10.1093/nar/gkg161
[27]  Klug, A. (2010) The Discovery of Zinc Fingers and Their Applications in Gene Regulation and Genome Manipulation. Annual Review of Biochemistry, 79, 213-231.
https://doi.org/10.1146/annurev-biochem-010909-095056
[28]  Rouhanifard, S.H., Mellis, I.A., Dunagin, M., Bayatpour, S., Jiang, C.L., Dardani, I., et al. (2018) ClampFISH Detects Individual Nucleic Acid Molecules Using Click Chemistry-Based Amplification. Nature Biotechnology, 37, 84-89.
https://doi.org/10.1038/nbt.4286
[29]  Studer, S., Hansen, D.A., Pianowski, Z.L., Mittl, P.R.E., Debon, A., Guffy, S.L., et al. (2018) Evolution of a Highly Active and Enantiospecific Metalloenzyme from Short Peptides. Science, 362, 1285-1288.
https://doi.org/10.1126/science.aau3744
[30]  Sievers, Q.L., Petzold, G., Bunker, R.D., Renneville, A., Slabicki, M., Liddicoat, B.J., et al. (2018) Defining the Human C2H2 Zinc Finger Degrome Targeted by Thalidomide Analogs through CRBN. Science, 362, eaat0572.
https://doi.org/10.1126/science.aat0572

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