Bioinformatics Analysis of Protein Homologues of Magnetotactic Bacteria Magnetosome Island Proteins in Human Proteome
Keywords:biogenic magnetic nanoparticles, biomineralization, oncological diseases, neurodegenerative diseases, proteins homologues, magnetosome island, magnetotactic bacteria
Background. The number of biogenic magnetic nanoparticles (BMN), present in human organs and tissues in the form of magnetite (ferrimagnetic iron oxide), increases in oncological and neurodegenerative diseases. Therefore, the study of homologues of BMN biomineralization proteins (mam-proteins) of magnetotaxis bacteria (MTB) in human proteome is relevant task. This concern is due primarily to the expediency of establishing patterns of changes in the expression of these proteins and searching for correlations with oncological and neurodegenerative diseases.
Objective. We are aimed to conduct the bioinformatic analysis of homologues of MTB mam-proteins in humans and to determine the patterns of changes in the expression of these proteins, as well as to search for their connections with the specified diseases. This will allow to identify the main candidate proteins (among the known homologues of MTB mam-proteins in humans) for experimental verification of their participation in the genetically programmed mechanism of BMN biosynthesis in humans.
Methods. The methods of comparative genomics were used, in particular the BLAST (Basic Local Alignment Search Tool) program of the NCBI database. Database tools were also used: NCBI Conserved Domain Search, The Cancer Genome Atlas database, Ensembl database.
Results. The bioinformatic analysis of 16 homologues of MTB mam-proteins in humans was carried out, namely: PEX5, ANAPC7, CDC23, CDC27 and SGTA – homologues of MamA in MTB; SLC30A4, SLC30A9, SLC39A3 and SLC39A4 – homologs of MamB and MamM in MTB; HTRA1, HTRA2, HTRA3 and HTRA4 – MamO and MamE homologues in MTB; SCRIB, PDZK1 and PDZD3 – MamE homologues in MTB. Using pairwise alignments, the degree of homology between the mam-proteins of the MTB magnetosome island and the corresponding human proteins was determined, conserved domains and their functions were determined, changes in their expression levels in cancer and normal conditions were determined by analyzing the relevant databases, and the metabolic pathways to which the data proteins are involved were analysed. The analysis of the obtained data allowed to assume the presence of the main homologues of the MTB mam-proteins of the magnetosome island in humans, which cause an increase in the level of BMN in oncological and neurodegenerative diseases, namely: an increase in the expression level of the proteins PEX5, ANAPC7 (homologs of MamA), SLC39A3, SLC39A4 (homologs of MamB and MamM), HTRA4 (MamO and MamE homolog) and SCRIB (MamE homolog).
Conclusions. The obtained data allow us to assume that the proteins PEX5, ANAPC7, SGTA, SLC39A3, SLC39A4, HTRA4 and SCRIB are the main homologues of the MTB mam-proteins in humans and cause an increase in the level of BMN in oncological and neurodegenerative diseases.
Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ. Magnetite biomineralization in the human brain. Proc Natl Acad Sci USA. 1992 Aug; 89(16):7683-7. DOI: 10.1073/pnas.89.16.7683
Gorobets SV, Medviediev O, Gorobets OY, Ivanchenko A. Biogenic magnetic nanoparticles in human organs and tissues. Prog Biophys Molec Biol. 2018 Jul;135:49-57. DOI: 10.1016/j.pbiomolbio.2018.01.010
Gorobets SV, Gorobets OY. Functions of biogenic magnetic nanoparticles in organisms. Funct Mater. 2012;19(1):18-26.
Gorobets OY, Gorobets SV, Gorobets YI. Biogenic magnetic nanoparticles. Biomineralization in prokaryotes and eukaryotes. In: Dekker Encyclopedia of Nanoscience and Nanotechnology. 3d ed. New York: CRC Press; 2013. p. 300-8.
Van de Walle A, Plan Sangnier A, Abou-Hassan A, Curcio A, Hémadi M, Menguy N, et al. Biosynthesis of magnetic nanoparticles from nano-degradation products revealed in human stem cells. Proc Natl Acad Sci U S A. 2019 Mar 5;116(10):4044-53. DOI: 10.1073/pnas.1816792116
Gorobets S, Gorobets O, Gorobets Y, Bulaievska M. Chain‐like structures of biogenic and nonbiogenic magnetic nanoparticles in vascular tissues. Bioelectromagnetics. 2022 Jan;43(2):119-43. DOI: 10.1002/bem.22390
Schübbe S, Würdemann C, Peplies J, Heyen U, Wawer C, Glöckner FO, et al. Transcriptional organization and regulation of magnetosome operons in Magnetospirillum gryphiswaldense. Appl Environ Microbiol. 2006 Sep;72(9):5757-65. DOI: 10.1128/AEM.00201-06
Hautot D, Pankhurst QA, Khan N, Dobson J. Preliminary evaluation of nanoscale biogenic magnetite in Alzheimer's disease brain tissue. Proc Biol Sci. 2003 Aug 7;270 Suppl 1(Suppl 1):S62-4. DOI: 10.1098/rsbl.2003.0012
Moos T, Morgan EH. The metabolism of neuronal iron and its pathogenic role in neurological disease: review. Ann N Y Acad Sci. 2004 Mar;1012(1):14-26. DOI: 10.1196/annals.1306.002
Bartzokis G, Tishler TA. MRI evaluation of basal ganglia ferritin iron and neurotoxicity in Alzheimer's and Huntingon's disease. Cell Mol Biol (Noisy-le-grand). 2000 Jun;46(4):821-33.
Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR. Copper, iron and zinc in Alzheimer’s disease senile plaques. J Neurol Sci. 1998 Jun;158(1):47-52. DOI: 10.1016/s0022-510x(98)00092-6
Brem F, Hirt AM, Winklhofer M, Frei K, Yonekawa Y, Wieser HG, et al. Magnetic iron compounds in the human brain: a comparison of tumour and hippocampal tissue. J R Soc Interface. 2006 Dec 22;3(11):833-41. DOI: 10.1098/rsif.2006.0133
Chekchun VF, Gorobets SV, Gorobets OY, Demianenko IV. Magnet-sensitive nanostructures of endogenous origin in Ehrlich carcinoma cells. Nanostruct Mater. 2011;2:102-9.
McKeown SR. Defining normoxia, physoxia and hypoxia in tumours-implications for treatment response. Br J Radiol. 2014 Mar;87(1035):20130676. DOI: 10.1259/bjr.20130676
Merelli A, Repetto M, Lazarowski A, Auzmendi J. Hypoxia, oxidative stress, and inflammation: three faces of neurodegenerative diseases. J Alzheimers Dis. 2021 Jun;82(s1):S109-26. DOI: 10.3233/JAD-201074
Medviediev O, Gorobets OY, Gorobets SV, Yadrykhins'ky VS. The prediction of biogenic magnetic nanoparticles biomineralization in human tissues and organs. J Phys Conf Ser. 2017 Oct;903:012002. DOI: 10.1088/1742-6596/903/1/012002
Komeili A. Molecular mechanisms of compartmentalization and biomineralization in magnetotactic bacteria. FEMS Microbiol Rev. 2012 Jan;36(1):232-55. DOI: 10.1111/j.1574-6976.2011.00315x
Lobry JR, Gautier C. Hydrophobicity, expressivity and aromaticity are the major trends of amino-acid usage in 999 Escherichia coli chromosome-encoded genes. Nucleic Acids Res. 1994 Aug;22(15):3174-80. DOI: 10.1093/nar/22.15.3174
Vihinen M, Torkkila E, Riikonen P. Accuracy of protein flexibility predictions. Proteins. 1994 Jun;19(2):141-9. DOI: 10.1002/prot.340190207
Guruprasad K, Reddy BV, Pandit MW. Correlation between stability of a protein and its dipeptide composition: a novel approach for predicting in vivo stability of a protein from its primary sequence. Protein Eng. 1990 Dec;4(2):155-61. DOI: 10.1093/protein/4.2.155
AM Lesk. Introduction to Bioinformatics. 4th ed. Oxford: University Press; 2005. 440 p.
Dobson J. Nanoscale biogenic iron oxides and neurodegenerative disease. FEBS Lett. 2001 May;496(1):1-5. DOI: 10.1016/s0014-5793(01)02386-9
Kubota S, Doi H, Koyano S, Tanaka K, Komiya H, Katsumoto A, et al. SGTA associates with intracellular aggregates in neurodegenerative diseases. Mol Brain. 2021 Mar 23;14(1):59. DOI: 10.1186/s13041-021-00770-1
Benarroch R, Austin JM, Ahmed F, Isaacson RL. The roles of cytosolic quality control proteins, SGTA and the BAG6 complex, in disease. In: Adv Protein Chem Struct Biol. Vol. 114. Elsevier; 2019. p. 265-313. DOI: 10.1016/bs.apcsb.2018.11.002
Feuillette S, Charbonnier C, Frebourg T, Campion D, Lecourtois M. A connected network of interacting proteins is involved in human-tau toxicity in drosophila. Front Neurosci. 2020 Feb;14:68. DOI: 10.3389/fnins.2020.00068
Skorko-Glonek J. HtrA protease family as therapeutic targets. Curr Pharm Des. 2013;19(6):977-1009. DOI: 10.2174/1381612811319060003
Zurawa-Janicka D, Skorko-Glonek J, Lipinska B. HtrA proteins as targets in therapy of cancer and other diseases. Expert Opin Ther Targets. 2010 Jul;14(7):665-79. DOI: 10.1517/14728222.2010.487867
Kawamoto Y. Accumulation of HtrA2/Omi in neuronal and glial inclusions in brains with alpha-synucleinopathies. J Neuropathol Exp Neurol. 2008 Oct;67(10):984-93. DOI: 10.1097/NEN.0b013e31818809f4
Bhuiyan MS, Fukunaga K. Mitochondrial serine protease HtrA2/Omi as a potential therapeutic target. Curr Drug Targets. 2009 Apr;10(4):372-83. DOI: 10.2174/138945009787846399
Goo HG, Rhim H, Kang S. Pathogenic role of serine protease HtrA2/Omi in neurodegenerative diseases. Curr Protein Pept Sci. 2017;18(7):746-57. DOI: 10.2174/1389203717666160311115750
Vargas DM, de Bastiani MA, Zimmer ER, Klamt F. Alzheimer's disease master regulators analysis: search for potential molecular targets and drug repositioning candidates. Alzheimers Res Ther. 2018 June;10(1):59. DOI: 10.1186/s13195-018-0394-7
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