Tuftelin Interacting Protein 11 (TFIP11) was identified as a critical human spliceosome assembly regulator, interacting with multiple proteins and localising in membrane-less organelles. However, a lack of structural information on TFIP11 limits the rationalisation of its biological role. TFIP11 is predicted as an intrinsically disordered protein (IDP), and more specifically concerning its N-terminal (N-TER) region. IDPs lack a defined tertiary structure, existing as a dynamic conformational ensemble, favouring protein-protein and protein-RNA interactions. IDPs are involved in liquid-liquid phase separation (LLPS), driving the formation of subnuclear compartments. Combining disorder prediction, molecular dynamics, and spectroscopy methods, this contribution shows the first evidence TFIP11 N-TER is a polyampholytic IDP, exhibiting a structural duality with the coexistence of ordered and disordered assemblies, depending on the ionic strength. Increasing the salt concentration enhances the protein conformational flexibility, presenting a more globule-like shape, and a fuzzier unstructured arrangement that could favour LLPS and protein-RNA interaction. The most charged and hydrophilic regions are the most impacted, including the G-Patch domain essential to TFIP11 function. This study gives a better understanding of the salt-dependent conformational behaviour of the N-TER TFIP11, supporting the hypothesis of the formation of different types of protein assembly, in line with its multiple biological roles.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Juniku, Blinera; Laboratory of Physical Chemistry of Biomolecules, UCPTS, University of Namur, Rue de Bruxelles 61, B-5000 Namur, Belgium, Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium, Namur Institute of Structured Matter (NISM), University of Namur, Namur, Belgium, GIGA-Molecular Biology of Diseases, Molecular Analysis of Gene Expression (MAGE) Laboratory, University of Liege, B34, Avenue de l'Hôpital, B-4000 Liège, Belgium
Mignon, Julien; Laboratory of Physical Chemistry of Biomolecules, UCPTS, University of Namur, Rue de Bruxelles 61, B-5000 Namur, Belgium, Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium, Namur Institute of Structured Matter (NISM), University of Namur, Namur, Belgium
Carême, Rachel; Laboratory of Physical Chemistry of Biomolecules, UCPTS, University of Namur, Rue de Bruxelles 61, B-5000 Namur, Belgium
Obeid, Anna Maria ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Mottet, Denis ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Monari, Antonio; Université Paris Cité and CNRS, ITODYS, F-75006, Paris, France
Michaux, Catherine; Laboratory of Physical Chemistry of Biomolecules, UCPTS, University of Namur, Rue de Bruxelles 61, B-5000 Namur, Belgium, Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium, Namur Institute of Structured Matter (NISM), University of Namur, Namur, Belgium. Electronic address: catherine.michaux@unamur.be
Language :
English
Title :
Intrinsic disorder and salt-dependent conformational changes of the N-terminal region of TFIP11 splicing factor.
Publication date :
30 July 2024
Journal title :
International Journal of Biological Macromolecules
B. J. and J. M. thank the Belgian National Fund for Scientific Research (F.R.S.-FNRS) for their FRIA (Fund for Research training in Industry and Agriculture) Doctoral grant and Research Fellow fellowship, respectively. A.M.O. and A.G. are PhD students supported by the University of Li\u00E8ge (Fonds Sp\u00E9ciaux Recherche) and the Belgian National Fund for Scientific Research (F.R.S.-FNRS), respectively. The authors are appreciative to the PTCI high-performance computing resource and the Research Unit in Biology of Micro-organisms of the University of Namur. The present research benefited from computational resources provided by the Consortium des \u00C9quipements de Calcul Intensif (C\u00C9CI), funded by the FNRS under grant n\u00B02.5020.11 and by the Walloon Region , and made available on Lucia, the Tier-1 supercomputer of the Walloon Region, infrastructure funded by the Walloon Region under the grant agreement n\u00B01910247 . C. M. and D. M. also thank the FNRS for their Senior Research Associate position. A. M. thanks ANR and CGI for their financial support of this work through Labex SEAM ANR 11 LABEX 086 , ANR 11 IDEX 05 02 . The support of the IdEx \u201C Universit\u00E9 Paris 2019 \u201D ANR-18-IDEX-0001 is also acknowledged. B. J. thanks Younes Bourenane Cherif for his precious help in designing the figures.
Ivanova, O.M., Anufrieva, K.S., Kazakova, A.N., Malyants, I.K., Shnaider, P.V., Lukina, M.M., Shender, V.O., Non-canonical functions of spliceosome components in cancer progression. Cell Death Dis., 14(2), 2023, 77, 10.1038/s41419-022-05470-9.
Yang, H., Beutler, B., Zhang, D., Emerging roles of spliceosome in cancer and immunity. Protein Cell 13:8 (2022), 559–579, 10.1007/s13238-021-00856-5.
Hsu, T.Y.-T., Simon, L.M., Neill, N.J., Marcotte, R., Sayad, A., Bland, C.S., Echeverria, G.V., Sun, T., Kurley, S.J., Tyagi, S., Karlin, K.L., Dominguez-Vidaña, R., Hartman, J.D., Renwick, A., Scorsone, K., Bernardi, R.J., Skinner, S.O., Jain, A., Orellana, M., Lagisetti, C., Golding, I., Jung, S.Y., Neilson, J.R., Zhang, X.H.-F., Cooper, T.A., Webb, T.R., Neel, B.G., Shaw, C.A., Westbrook, T.F., The Spliceosome Is a Therapeutic Vulnerability in MYC-Driven Cancer. Nature 525:7569 (2015), 384–388, 10.1038/nature14985.
Dvinge, H., Guenthoer, J., Porter, P.L., Bradley, R.K., RNA components of the spliceosome regulate tissue- and cancer-specific alternative splicing. Genome Res. 29:10 (2019), 1591–1604, 10.1101/gr.246678.118.
An, J., Luo, Z., An, W., Cao, D., Ma, J., Liu, Z., Identification of spliceosome components pivotal to breast cancer survival. RNA Biol. 18:6 (2021), 833–842, 10.1080/15476286.2020.1822636.
Oltean, S., Bates, D.O., Hallmarks of alternative splicing in cancer. Oncogene 33:46 (2014), 5311–5318, 10.1038/onc.2013.533.
Coltri, P.P., dos Santos, M.G.P., da Silva, G.H.G., Splicing and cancer: challenges and opportunities. WIREs RNA, 10(3), 2019, 10.1002/wrna.1527.
Uversky, V.N., Intrinsically Disordered Proteins and Their “Mysterious” (Meta)Physics. Front. Phys., 7, 2019, 10, 10.3389/fphy.2019.00010.
Duchemin, A., O'Grady, T., Hanache, S., Mereau, A., Thiry, M., Wacheul, L., Michaux, C., Perpète, E., Hervouet, E., Peixoto, P., Ernst, F.G.M., Audic, Y., Dequiedt, F., Lafontaine, D.L.J., Mottet, D., DHX15-independent roles for TFIP11 in U6 SnRNA modification, U4/U6.U5 tri-SnRNP assembly and pre-MRNA splicing fidelity. Nat. Commun. 12:1 (2021), 1–20, 10.1038/s41467-021-26932-2.
Deckert, J., Hartmuth, K., Boehringer, D., Behzadnia, N., Will, C.L., Kastner, B., Stark, H., Urlaub, H., Lührmann, R., Protein composition and electron microscopy structure of affinity-purified human Spliceosomal B complexes isolated under physiological conditions. Mol. Cell. Biol. 26:14 (2006), 5528–5543, 10.1128/MCB.00582-06.
Mouffok, S., Capeyrou, R., Belhabich-Baumas, K., Joret, C., Henras, A.K., Humbert, O., Henry, Y., The G-patch activators Pfa1 and PINX1 exhibit different modes of interaction with the Prp43 RNA helicase. RNA Biol. 18:4 (2021), 510–522, 10.1080/15476286.2020.1818458.
Ahn, E.E.-Y., Higashi, T., Yan, M., Matsuura, S., Hickey, C.J., Lo, M.-C., Shia, W.-J., DeKelver, R.C., Zhang, D.-E., SON protein regulates GATA-2 through transcriptional control of the MicroRNA 23a∼27a∼24-2 cluster*. J. Biol. Chem. 288:8 (2013), 5381–5388, 10.1074/jbc.M112.447227.
Aksaas, A. K.; Larsen, A. C. V; Rogne, M.; Rosendal, K.; Kvissel, A.-K.; Skålhegg, B. S. G-patch domain and KOW motifs-containing protein, GPKOW; a nuclear RNA-binding protein regulated by protein kinase A. J. Mol. Signal 2011, 6, 10. doi: https://doi.org/10.1186/1750-2187-6-10.
Robert-Paganin, J., Réty, S., Leulliot, N., Regulation of DEAH/RHA helicases by G-patch proteins. Biomed. Res. Int. 2015 (2015), 1–9, 10.1155/2015/931857.
Bohnsack, K.E., Ficner, R., Bohnsack, M.T., Jonas, S., Regulation of DEAH-box RNA helicases by G-patch proteins. Biol. Chem. 402:5 (2021), 561–579, 10.1515/hsz-2020-0338.
Wen, X., Tannukit, S., Paine, M.L., TFIP11 interacts with MDEAH9, an RNA helicase involved in spliceosome disassembly. Int. J. Mol. Sci. 9:11 (2008), 2105–2113, 10.3390/ijms9112105.
Cascarina, S.M., Elder, M.R., Ross, E.D., Atypical Structural Tendencies among Low-Complexity Domains in the Protein Data Bank Proteome. PLoS Comput. Biol., 16(1), 2020, 10.1371/journal.pcbi.1007487.
Selig, E.E., Bhura, R., White, M.R., Akula, S., Hoffman, R.D., Tovar, C.N., Xu, X., Booth, R.E., Libich, D.S., Biochemical and Biophysical Characterization of the Nucleic Acid Binding Properties of the RNA/DNA Binding Protein EWS. Biopolymers, 114(5), 2023, 10.1002/bip.23536.
Lye, Y.S., Chen, Y., TAR DNA-binding protein 43 oligomers in physiology and pathology. IUBMB Life 74:8 (2022), 794–811, 10.1002/iub.2603.
Lee, J., Cho, H., Kwon, I., Phase separation of low-complexity domains in cellular function and disease. Exp. Mol. Med. 54:9 (2022), 1412–1422, 10.1038/s12276-022-00857-2.
Fernández-Alvarez, A.J., Thomas, M.G., Giudice, J., Boccaccio, G.L., Active Regulation Mechanisms of LLPS and MLOs Biogenesis. Droplets of Life, 2023, Elsevier, 337–373, 10.1016/B978-0-12-823967-4.00005-1.
Wohl, S., Jakubowski, M., Zheng, W., Salt-dependent conformational changes of intrinsically disordered proteins. J. Phys. Chem. Lett. 12:28 (2021), 6684–6691, 10.1021/acs.jpclett.1c01607.
Maity, H., Baidya, L., Reddy, G., Salt-induced transitions in the conformational ensembles of intrinsically disordered proteins. J. Phys. Chem. B 126:32 (2022), 5959–5971, 10.1021/acs.jpcb.2c03476.
Williams, R.M., Obradovi, Z., Mathura, V., Braun, W., Garner, E.C., Takayama, S., Brown, C.J., Dunker, A.K., The protein non-folding problem: amino acid determinants of intrinsic order and disorder. Pac Symp Biocomp., 2001, 89–100.
Peng, K., Vucetic, S., Radivojac, P., Brown, C.J., Dunker, A.K., Obradovic, Z., Optimizing long intrinsic disorder predictors with protein evolutionary information. J. Bioinform. Comput. Biol. 3:1 (2005), 35–60, 10.1142/s0219720005000886.
Garner, Romero, Dunker, Brown, Obradovic, Predicting binding regions within disordered proteins. Genome Inform Ser Workshop Genome Inform 10 (1999), 41–50.
Erdos, G., Pajkos, M., Dosztányi, Z., IUPred3: prediction of protein disorder enhanced with unambiguous experimental annotation and visualization of evolutionary conservation. Nucleic Acids Res. 49 (2021), 297–303, 10.1093/nar/gkab408.
Ishida, T., Kinoshita, K., PrDOS: prediction of disordered protein regions from amino acid sequence. Nucleic Acids Res. 35 (2007), 460–464, 10.1093/nar/gkm363.
Walsh, I., Martin, A.J.M., Di Domenico, T., Tosatto, S.C.E., Espritz: accurate and fast prediction of protein disorder. Bioinformatics 28:4 (2012), 503–509, 10.1093/bioinformatics/btr682.
Dass, R., Mulder, F.A.A., Nielsen, J.T., ODiNPred: Comprehensive Prediction of Protein Order and Disorder. Sci. Rep., 10(1), 2020, 10.1038/s41598-020-71716-1.
Emenecker, R.J., Griffith, D., Holehouse, A.S., Metapredict: a fast, accurate, and easy-to-use predictor of consensus disorder and structure. Biophys. J. 120:20 (2021), 4312–4319, 10.1016/j.bpj.2021.08.039.
Bernhofer, M., Dallago, C., Karl, T., Satagopam, V., Heinzinger, M., Littmann, M., Olenyi, T., Qiu, J., Schütze, K., Yachdav, G., Ashkenazy, H., Ben-Tal, N., Bromberg, Y., Goldberg, T., Kajan, L., O'Donoghue, S., Sander, C., Schafferhans, A., Schlessinger, A., Vriend, G., Mirdita, M., Gawron, P., Gu, W., Jarosz, Y., Trefois, C., Steinegger, M., Schneider, R., Rost, B., PredictProtein - Predicting Protein Structure and Function for 29 Years. Nucleic Acids Res. 49:1 (2021), 535–540, 10.1093/nar/gkab354.
Høie, M.H., Kiehl, E.N., Petersen, B., Nielsen, M., Winther, O., Nielsen, H., Hallgren, J., Marcatili, P., NetSurfP-3.0: accurate and fast prediction of protein structural features by protein language models and deep learning. Nucleic Acids Res. 50 (2022), 510–515, 10.1093/nar/gkac439.
Hu, G., Katuwawala, A., Wang, K., Wu, Z., Ghadermarzi, S., Gao, J., Kurgan, L., FlDPnn: Accurate Intrinsic Disorder Prediction with Putative Propensities of Disorder Functions. Nat. Commun., 12(1), 2021, 10.1038/s41467-021-24773-7.
Orlando, G., Raimondi, D., Codicè, F., Tabaro, F., Vranken, W., Prediction of Disordered Regions in Proteins with Recurrent Neural Networks and Protein Dynamics. J. Mol. Biol., 434(12), 2022, 10.1016/j.jmb.2022.167579.
Dayhoff, G. W.; Uversky, V. N. Rapid Prediction and Analysis of Protein Intrinsic Disorder. Protein Science 2022, 31 (12), 61a. doi: https://doi.org/10.1002/pro.4496.
Holehouse, A.S., Das, R.K., Ahad, J.N., Richardson, M.O.G., Pappu, R.V., CIDER: resources to analyze sequence-ensemble relationships of intrinsically disordered proteins. Biophys. J. 112:1 (2017), 16–21, 10.1016/j.bpj.2016.11.3200.
Malhis, N., Jacobson, M., Gsponer, J., MoRFchibi SYSTEM: software tools for the identification of MoRFs in protein sequences. Nucleic Acids Res. 44:W1 (2016), W488–W493, 10.1093/nar/gkw409.
Abraham, M.J., Murtola, T., Schulz, R., Páll, S., Smith, J.C., Hess, B., Lindah, E., Gromacs: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1–2 (2015), 19–25, 10.1016/j.softx.2015.06.001.
Maier, J.A., Martinez, C., Kasavajhala, K., Wickstrom, L., Hauser, K.E., Simmerling, C., Ff14SB: improving the accuracy of protein side chain and backbone parameters from Ff99SB. J. Chem. Theory Comput. 11:8 (2015), 3696–3713, 10.1021/acs.jctc.5b00255.
Izadi, S., Anandakrishnan, R., Onufriev, A.V., Building water models: a different approach. J. Phys. Chem. Lett. 5:21 (2014), 3863–3871, 10.1021/jz501780a.
Mu, J., Liu, H., Zhang, J., Luo, R., Chen, H.-F., Recent force field strategies for intrinsically disordered proteins. J. Chem. Inf. Model. 61:3 (2021), 1037–1047, 10.1021/acs.jcim.0c01175.
Hopkins, C.W., Le Grand, S., Walker, R.C., Roitberg, A.E., Long-time-step molecular dynamics through hydrogen mass repartitioning. J. Chem. Theory Comput. 11:4 (2015), 1864–1874, 10.1021/ct5010406.
Petersen, H.G., Accuracy and efficiency of the particle mesh Ewald method. J. Chem. Phys. 103:9 (1995), 3668–3679, 10.1063/1.470043.
Yuan, S., Chan, H.C.S., Hu, Z., Using PyMOL as a Platform for Computational Drug Design. WIREs Computational Molecular Science, 7(2), 2017, 10.1002/wcms.1298.
Humphrey, W., Dalke, A., Schulten, K., VMD: Visual Molecular Dynamics. J. Mol. Graph. 14:1 (1996), 33–38, 10.1016/0263-7855(96)00018-5.
Hansen, J.C., Lu, X., Ross, E.D., Woody, R.W., Intrinsic protein disorder, amino acid composition, and histone terminal domains. J. Biol. Chem. 281:4 (2006), 1853–1856, 10.1074/jbc.R500022200.
Xue, B., Oldfield, C.J., Dunker, A.K., Uversky, V.N., CDF it all: consensus prediction of intrinsically disordered proteins based on various cumulative distribution functions. FEBS Lett. 583:9 (2009), 1469–1474, 10.1016/j.febslet.2009.03.070.
Xue, B., Oldfield, C.J., Dunker, A.K., Uversky, V.N., CDF it all: consensus prediction of intrinsically disordered proteins based on various cumulative distribution functions. FEBS Lett. 583:9 (2009), 1469–1474, 10.1016/j.febslet.2009.03.070.
Uversky, V.N., Gillespie, J.R., Fink, A.L., Why are “natively unfolded” proteins unstructured under physiologic conditions?. Proteins: Structure, Function and Genetics 41:3 (2000), 415–427, 10.1002/1097-0134(20001115)41:3<415::AID-PROT130>3.0.CO;2-7.
Das, R.K., Pappu, R.V., Conformations of intrinsically disordered proteins are influenced by linear sequence distributions of oppositely charged residues. Proc. Natl. Acad. Sci. U. S. A. 110:33 (2013), 13392–13397, 10.1073/pnas.1304749110.
Das, R.K., Ruff, K.M., Pappu, R.V., Relating sequence encoded information to form and function of intrinsically disordered proteins. Curr. Opin. Struct. Biol. 32 (2015), 102–112, 10.1016/j.sbi.2015.03.008.
Martin, E.W., Holehouse, A.S., Grace, C.R., Hughes, A., Pappu, R.V., Mittag, T., Sequence determinants of the conformational properties of an intrinsically disordered protein prior to and upon multisite phosphorylation. J. Am. Chem. Soc. 138:47 (2016), 15323–15335, 10.1021/jacs.6b10272.
Morris, O.M., Torpey, J.H., Isaacson, R.L., Intrinsically Disordered Proteins: Modes of Binding with Emphasis on Disordered Domains. Open Biol., 11(10), 2021, 10.1098/rsob.210222.
Tannukit, S., Crabb, T.L., Hertel, K.J., Wen, X., Jans, D.A., Paine, M.L., Identification of a novel nuclear localization signal and speckle-targeting sequence of Tuftelin-interacting protein 11, a splicing factor involved in spliceosome disassembly. Biochem. Biophys. Res. Commun. 390:3 (2009), 1044–1050, 10.1016/j.bbrc.2009.10.111.
Studer, M.K., Ivanović, L., Weber, M.E., Marti, S., Jonas, S., Structural basis for DEAH-helicase activation by G-patch proteins. Proc. Natl. Acad. Sci. 117:13 (2020), 7159–7170, 10.1073/pnas.1913880117.
Dong, X., Bera, S., Qiao, Q., Tang, Y., Lao, Z., Luo, Y., Gazit, E., Wei, G., Liquid-liquid phase separation of tau protein is encoded at the monomeric level. J. Phys. Chem. Lett. 12:10 (2021), 2576–2586, 10.1021/acs.jpclett.1c00208.
Ivankov, D.N., Bogatyreva, N.S., Lobanov, M.Y., Galzitskaya, O.V., Coupling between Properties of the Protein Shape and the Rate of Protein Folding. PLoS One, 4(8), 2009, 10.1371/journal.pone.0006476.
Bianchi, G., Longhi, S., Grandori, R., Brocca, S., Relevance of electrostatic charges in compactness, aggregation, and phase separation of intrinsically disordered proteins. Int. J. Mol. Sci., 21(17), 2020, 6208, 10.3390/ijms21176208.
Maity, H., Baidya, L., Reddy, G., Salt-induced transitions in the conformational ensembles of intrinsically disordered proteins. J. Phys. Chem. B 126:32 (2022), 5959–5971, 10.1021/acs.jpcb.2c03476.
Majumdar, A., Dogra, P., Maity, S., Mukhopadhyay, S., Liquid-liquid phase separation is driven by large-scale conformational unwinding and fluctuations of intrinsically disordered protein molecules. J. Phys. Chem. Lett. 10:14 (2019), 3929–3936, 10.1021/acs.jpclett.9b01731.
Studer, M.K., Ivanović, L., Weber, M.E., Marti, S., Jonas, S., Structural basis for DEAH-helicase activation by G-patch proteins. Proc. Natl. Acad. Sci. 117:13 (2020), 7159–7170, 10.1073/pnas.1913880117.
Chen, P., Lin, C., Lee, C., Jan, H., Chan, S.I., Effects of turn residues in directing the formation of the Β-sheet and in the stability of the Β-sheet. Protein Sci. 10:9 (2001), 1794–1800, 10.1110/ps.49001.
Mignon, J., Mottet, D., Leyder, T., Uversky, V.N., Perpète, E.A., Michaux, C., Structural characterisation of amyloidogenic intrinsically disordered zinc finger protein isoforms DPF3b and DPF3a. Int. J. Biol. Macromol. 218:June (2022), 57–71, 10.1016/j.ijbiomac.2022.07.102.
Vilar, M., Chou, H.-T., Lührs, T., Maji, S.K., Riek-Loher, D., Verel, R., Manning, G., Stahlberg, H., Riek, R., The fold of α-synuclein fibrils. Proc. Natl. Acad. Sci. 105:25 (2008), 8637–8642, 10.1073/pnas.0712179105.
Vivian, J.T., Callis, P.R., Mechanisms of tryptophan fluorescence shifts in proteins. Biophys. J. 80:5 (2001), 2093–2109, 10.1016/S0006-3495(01)76183-8.
Lakowicz, J.R., Principles of Fluorescence Spectroscopy. Third Edit, 2006, Springer Science.
Mignon, J., Leyder, T., Mottet, D., Uversky, V.N., Michaux, C., In-Depth Investigation of the Effect of PH on the Autofluorescence Properties of DPF3b and DPF3a Amyloid Fibrils. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2024, 313, 10.1016/j.saa.2024.124156.
Chiesa, G., Kiriakov, S., Khalil, A.S., Protein assembly systems in natural and synthetic biology. BMC Biol., 18(1), 2020, 35, 10.1186/s12915-020-0751-4.
Wegmann, S., Eftekharzadeh, B., Tepper, K., Zoltowska, K.M., Bennett, R.E., Dujardin, S., Laskowski, P.R., MacKenzie, D., Kamath, T., Commins, C., Vanderburg, C., Roe, A.D., Fan, Z., Molliex, A.M., Hernandez-Vega, A., Muller, D., Hyman, A.A., Mandelkow, E., Taylor, J.P., Hyman, B.T., Tau Protein Liquid–Liquid Phase Separation Can Initiate Tau Aggregation. EMBO J, 37(7), 2018, 10.15252/embj.201798049.
Fuxreiter, M., Tompa, P., Fuzzy Complexes: A More Stochastic View of Protein Function. 2012, 1–14, 10.1007/978-1-4614-0659-4_1.
Tsoi, P.S., Quan, M.D., Ferreon, J.C., Ferreon, A.C.M., Aggregation of disordered proteins associated with neurodegeneration. Int. J. Mol. Sci., 24(4), 2023, 3380, 10.3390/ijms24043380.
Christian, H., Hofele, R.V., Urlaub, H., Ficner, R., Insights into the activation of the helicase Prp43 by biochemical studies and structural mass spectrometry. Nucleic Acids Res. 42:2 (2014), 1162–1179, 10.1093/nar/gkt985.
Hornbeck, P.V., Kornhauser, J.M., Tkachev, S., Zhang, B., Skrzypek, E., Murray, B., Latham, V., Sullivan, M., PhosphoSitePlus: a comprehensive resource for investigating the structure and function of experimentally determined post-translational modifications in man and mouse. Nucleic Acids Res. 40:D1 (2012), D261–D270, 10.1093/nar/gkr1122.
Lundby, A., Lage, K., Weinert, B.T., Bekker-Jensen, D.B., Secher, A., Skovgaard, T., Kelstrup, C.D., Dmytriyev, A., Choudhary, C., Lundby, C., Olsen, J.V., Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns. Cell Rep. 2:2 (2012), 419–431, 10.1016/j.celrep.2012.07.006.
Tannukit, S., Crabb, T.L., Hertel, K.J., Wen, X., Jans, D.A., Paine, M.L., Identification of a novel nuclear localization signal and speckle-targeting sequence of Tuftelin-interacting protein 11, a splicing factor involved in spliceosome disassembly. Biochem. Biophys. Res. Commun. 390:3 (2009), 1044–1050, 10.1016/j.bbrc.2009.10.111.
Švec, M., Bauerová, H., Pichová, I., Konvalinka, J., Strisovsky, K., Proteinases of betaretroviruses bind single-stranded nucleic acids through a novel interaction module, the G-patch. FEBS Lett. 576:1–2 (2004), 271–276, 10.1016/j.febslet.2004.09.010.
Nishi, H., Fong, J.H., Chang, C., Teichmann, S.A., Panchenko, A.R., Regulation of protein–protein binding by coupling between phosphorylation and intrinsic disorder: analysis of human protein complexes. Mol. Biosyst., 9(7), 2013, 1620, 10.1039/c3mb25514j.
Guo, A., Gu, H., Zhou, J., Mulhern, D., Wang, Y., Lee, K.A., Yang, V., Aguiar, M., Kornhauser, J., Jia, X., Ren, J., Beausoleil, S.A., Silva, J.C., Vemulapalli, V., Bedford, M.T., Comb, M.J., Immunoaffinity enrichment and mass spectrometry analysis of protein methylation. Mol. Cell. Proteomics 13:1 (2014), 372–387, 10.1074/mcp.O113.027870.
Larsen, S.C., Sylvestersen, K.B., Mund, A., Lyon, D., Mullari, M., Madsen, M.V., Daniel, J.A., Jensen, L.J., Nielsen, M.L., Proteome-Wide Analysis of Arginine Monomethylation Reveals Widespread Occurrence in Human Cells. Sci. Signal, 9(443), 2016, 10.1126/scisignal.aaf7329.
Musiani, D., Bok, J., Massignani, E., Wu, L., Tabaglio, T., Ippolito, M.R., Cuomo, A., Ozbek, U., Zorgati, H., Ghoshdastider, U., Robinson, R.C., Guccione, E., Bonaldi, T., Proteomics Profiling of Arginine Methylation Defines PRMT5 Substrate Specificity. Sci. Signal, 12(575), 2019, 10.1126/scisignal.aat8388.
Nadassy, K., Wodak, S.J., Janin, J., Structural features of protein−nucleic acid recognition sites. Biochemistry 38:7 (1999), 1999–2017, 10.1021/bi982362d.
Thapar, R., Structural basis for regulation of RNA-binding proteins by phosphorylation. ACS Chem. Biol. 10:3 (2015), 652–666, 10.1021/cb500860x.
Chatrikhi, R., Wang, W., Gupta, A., Loerch, S., Maucuer, A., Kielkopf, C.L., SF1 phosphorylation enhances specific binding to U2AF 65 and reduces binding to 3′-splice-site RNA. Biophys. J. 111:12 (2016), 2570–2586, 10.1016/j.bpj.2016.11.007.
Van Roey, K., Uyar, B., Weatheritt, R.J., Dinkel, H., Seiler, M., Budd, A., Gibson, T.J., Davey, N.E., Short linear motifs: ubiquitous and functionally diverse protein interaction modules directing cell regulation. Chem. Rev. 114:13 (2014), 6733–6778, 10.1021/cr400585q.
Kumar, M., Michael, S., Alvarado-Valverde, J., Mészáros, B., Sámano-Sánchez, H., Zeke, A., Dobson, L., Lazar, T., Örd, M., Nagpal, A., Farahi, N., Käser, M., Kraleti, R., Davey, N.E., Pancsa, R., Chemes, L.B., Gibson, T.J., The eukaryotic linear motif resource: 2022 release. Nucleic Acids Res. 50:D1 (2022), D497–D508, 10.1093/nar/gkab975.
Parolini, F., Tira, R., Barracchia, C.G., Munari, F., Capaldi, S., D'Onofrio, M., Assfalg, M., Ubiquitination of Alzheimer's-related tau protein affects liquid-liquid phase separation in a site- and cofactor-dependent manner. Int. J. Biol. Macromol. 201 (2022), 173–181, 10.1016/j.ijbiomac.2021.12.191.
Dao, T.P., Kolaitis, R.-M., Kim, H.J., O'Donovan, K., Martyniak, B., Colicino, E., Hehnly, H., Taylor, J.P., Castañeda, C.A., Ubiquitin Modulates Liquid-Liquid Phase Separation of UBQLN2 via Disruption of Multivalent Interactions. Mol. Cell 69:6 (2018), 965–978.e6, 10.1016/j.molcel.2018.02.004.
Li, J., Zhu, K., Gu, A., Zhang, Y., Huang, S., Hu, R., Hu, W., Lei, Q.-Y., Wen, W., Feedback Regulation of Ubiquitination and Phase Separation of HECT E3 Ligases. Proceedings of the National Academy of Sciences, 120 (33), 2023, 10.1073/pnas.2302478120.
Dao, T.P., Castañeda, C.A., Ubiquitin-Modulated Phase Separation of Shuttle Proteins: Does Condensate Formation Promote Protein Degradation?. BioEssays, 42(11), 2020, 10.1002/bies.202000036.
