Structural Characterization and Functional Interaction Analysis of Radiation Induced Protein Flt3 in Human and Mouse
DOI:
https://doi.org/10.31305/rrijm.2023.v08.n03.010Keywords:
Flt3L, radiation exposure, biomarkers, GOR IVAbstract
Increasing risk of radiation exposure can be due to various reasons such as terrorist attacks, detonation of nuclear reactors, nuclear weapons, as well as acute radiation exposure on large scale poses high risk to humankind. Therefore, there is a critical need of identification and authentication of fast and early-response radiation induced harm biomarkers to distinguish between exposed and non-exposed individuals on a large-scale basis. This study deals with structural characterization of radiation induced proteins that are probable biomarkers such as Flt3L using database tools such as prot-param for physio-chemical properties, GOR IV to predict the secondary structure, swiss modelling for 3D model of protein, stitch and string analysis for protein-chemical interaction and protein-protein interaction respectively. In-silico analysis showcasing, protein Flt3L physical parameters such as theoretical PI 8.72, hydrophobicity 0.100, aliphatic index 111.81. Secondary structure, alpha helix 41.38%, extended strand 11.64%. Homology modelling showing sequence identity 74.26%, coverage 0.50 and range 1-101. In stich, Flt3 activating KITLG and showing binding affinity to Zn molecule. Identification of protein-protein interacting functional partner of Flt3L using string shows interactions with polyubiquitin-C (UBC), KITLG, Nras proto onco genes, etc, it showed experimental evidence of Flt3L and KITLG protein. Hence, by using in-silico analysis we can perform a preliminary study to predict the structures and chemical interaction of potential radiation induced probable biomarkers that can be utilized for rapid detection of radiation exposure and drugdiscovery.
References
CDC (2022) What is Radiation? In: Cent. Dis. Control Prev. https://www.cdc.gov/nceh/radiation/what_is.html. Accessed 23 Jun2022
Reisz JA, Bansal N, Qian J, et al (2014) Effects of Ionizing Radiation on Biological Molecules— Mechanisms of Damage and Emerging Methods of Detection. Antioxid Redox Signal21:260–292. https://doi.org/10.1089/ars.2013.5489
Borrego-Soto G, Ortiz-López R, Rojas-Martínez A (2015) Ionizing radiation-induced DNA injury and damage detection in patients with breast cancer. Genet Mol Biol 38:420–432. https://doi.org/10.1590/S1415-475738420150019
Nita M, Grzybowski A (2016) The Role of the Reactive Oxygen Species and Oxidative Stress in the Pathomechanism of the Age-Related Ocular Diseases and Other Pathologies of the Anterior and Posterior Eye Segments in Adults. Oxid Med Cell Longev 2016:3164734. https://doi.org/10.1155/2016/3164734
Schmidt-Ullrich R, Dent P, Grant S, et al (2000) Signal Transduction and Cellular Radiation Responses. Radiat Res 153:245–57.https://doi.org/10.1667/0033- 7587(2000)153[0245:STACRR]2.0.CO;2
Pickering AndrewM, Davies KelvinJA (2012) Degradation of Damaged Proteins - The Main Function of the 20S Proteasome. Prog Mol BiolTransl Sci 109:227–248. https://doi.org/10.1016/B978-0-12-397863-9.00006-7
Mullenders LHF (2018) Solar UV damage to cellular DNA: from mechanisms to biological effects. PhotochemPhotobiol Sci Off J EurPhotochem Assoc Eur Soc Photobiol 17:1842–1852. https://doi.org/10.1039/c8pp00182k
Maier P, Hartmann L, Wenz F, Herskind C (2016) Cellular Pathways in Response to Ionizing Radiation and Their Targetability for TumorRadiosensitization. Int J Mol Sci 17:102. https://doi.org/10.3390/ijms17010102
Huang R-X, Zhou P-K (2020) DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer. Signal Transduct Target Ther 5:1–27. https://doi.org/10.1038/s41392-020-0150-x
HEIN AL, OUELLETTE MM, YAN Y (2014) Radiation-induced signaling pathways that promote cancercellsurvival(Review).IntJOncol45:1813–1819.https://doi.org/10.3892/ijo.2014.2614
Gao L, Zheng H, Cai Q, Wei L (2020) Autophagy and Tumour Radiotherapy. Adv Exp Med Biol 1207:375–387.https://doi.org/10.1007/978-981-15-4272-5_25
Dietz A, Gomolka M, Moertl S, Subedi P (2020) Ionizing Radiation Protein Biomarkers in Normal Tissue and Their Correlation to Radiosensitivity: Protocol for a Systematic Review. J Pers Med 11:3.https://doi.org/10.3390/jpm11010003
Jarosz-BiejM,SmolarczykR,CichońT,KułachN(2019)TumorMicroenvironmentasA“Game Changer”inCancerRadiotherapy.IntJMolSci20:E3212.https://doi.org/10.3390/ijms20133212
Ossetrova NI, Sandgren DJ, Blakely WF (2014) Protein biomarkers for enhancement of radiation dose and injury assessment in nonhuman primate total-body irradiation model. RadiatProt Dosimetry 159:61–76.https://doi.org/10.1093/rpd/ncu165
Lee Y, Pujol Canadell M, Shuryak I, et al (2018) Candidate protein markers for radiation biodosimetry in the hematopoietically humanized mouse model. Sci Rep 8:13557. https://doi.org/10.1038/s41598-018-31740-8
Quintens R, Baatout S, Moreels M (2020) Assessment of Radiosensitivity and Biomonitoring of Exposure to Space Radiation. In: Choukèr A (ed) Stress Challenges and Immunity in Space: From Mechanisms to Monitoring and Preventive Strategies. Springer International Publishing, Cham, pp519–533
Nesseler JP, Schaue D, McBride WH, Nickers P (2018) [Inflammatory and immune biomarkers of radiation response]. Cancer Radiother J Soc FrancaiseRadiother Oncol 22:180–192. https://doi.org/10.1016/j.canrad.2017.09.007
Ouerhani A, Chiappetta G, Souiai O, et al (2019) Investigation of serum proteome homeostasis during radiation therapy by a quantitative proteomics approach. Biosci Rep 39:BSR20182319. https://doi.org/10.1042/BSR20182319
Tremblay RG, Sikorska M, Sandhu JK, et al (2010) Differentiation of mouse Neuro 2A cells into dopamine neurons. J Neurosci Methods 186:60–67. https://doi.org/10.1016/j.jneumeth.2009.11.004
Neuro-2a | ATCC. https://www.atcc.org/products/ccl-131. Accessed 23 Jun2022
Persson B (2000) Bioinformatics in protein analysis. EXS88:215–231. https://doi.org/10.1007/978-3-0348-8458-7_14
Proteomics C Bioinformatics for Protein. In: Creat. Proteomics. https://www.creative- proteomics.com/services/bioinformatics-for-protein.htm. Accessed 23 Jun2022
ExPASy - ProtParam documentation. https://web.expasy.org/protparam/protparam-doc.html. Accessed 23 Jun2022
Kouza M, Faraggi E, Kolinski A, Kloczkowski A (2017) The GOR Method of Protein Secondary Structure Prediction and Its Application as a Protein Aggregation Prediction Tool. Methods Mol Biol Clifton NJ 1484:7–24.https://doi.org/10.1007/978-1-4939-6406-2_2
Protein Secondary Structure Prediction Based on Data Partition and Semi-Random Subspace Method | Scientific Reports. https://www.nature.com/articles/s41598-018-28084-8. Accessed 23 Jun2022
Waterhouse A, Bertoni M, Bienert S, et al (2018) SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res 46:W296–W303. https://doi.org/10.1093/nar/gky427
M B, S B, A W, et al (2014) SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res 42:.https://doi.org/10.1093/nar/gku340
Bienert S, Waterhouse A, de Beer TAP, et al (2017) The SWISS-MODEL Repository-new features and functionality. Nucleic Acids Res 45:D313–D319.https://doi.org/10.1093/nar/gkw1132
Help/STITCH: chemical association networks.http://stitch.embl.de/cgi/help.pl?UserId=2c2Xpb2BDQUX&sessionId=K0qRO0qrX6PX. Accessed 23 Jun2022
STITCH 5: augmenting protein-chemical interaction networks with tissue and affinity data - PubMed. https://pubmed.ncbi.nlm.nih.gov/26590256/. Accessed 23 Jun2022
Imperiale BR, Nieves C, Mancino B, et al (2018) String test: A new tool for tuberculosis diagnosis and drug-resistance detection in children. Int J Mycobacteriology 7:162–166. https://doi.org/10.4103/ijmy.ijmy_54_18
Help - STRING functional protein association networks. https://string- db.org/cgi/help?sessionId=bbXyvm0yv81x. Accessed 23 Jun2022
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an open access article under the CC BY-NC-ND license Creative Commons Attribution-Noncommercial 4.0 International (CC BY-NC 4.0).