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Protein & Peptide Letters

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ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

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Research Article

Insights into the Dynamic Fluctuations of the Protein HPV16 E1 and Identification of Motifs by Using Elastic Network Modeling

Author(s): Rabbiah Malik* and Sahar Fazal

Volume 28, Issue 9, 2021

Published on: 15 April, 2021

Page: [1061 - 1070] Pages: 10

DOI: 10.2174/0929866528666210415114858

Price: $65

Abstract

Background: Cancers of cervix, head and neck regions have been found to be associated with Human Papilloma Virus (HPV) infection. E1 protein makes an important papillomavirus replication factor. Among the ORFs of papillomaviruses, the most conserved sequence is that of the E1 ORF. It is the viral helicase with being a member of class of ATPases associated with diverse cellular activities (AAA+) helicases. The interactions of E1 with human DNA and proteins occurs in the presence of short linear peptide motifs on E1 identical to those on human proteins.

Methods: Different Motifs were identified on HPV16 E1 by using ELMs. Elastic network models were generated by using 3D structures of E1. Their dynamic fluctuations were analyzed on the basis of B factors, correlation analysis and deformation energies.

Results: 3 motifs were identified on E1 which can interact with Cdk and Cyclin domains of human proteins. 11 motifs identified on E1 have their CDs of Pkinase on human proteins. LIG_MYND_2 has been identified as involved in stabilizing interaction of E1 with Hsp40 and Hsp70. These motifs and amino acids comprising these motifs play a major role in maintaining interactions with human proteins, ultimately causing infections leading to cancers.

Conclusion: Our study identified various motifs on E1 which interact with specific counter domains found in human proteins, already reported having the interactions with E1. We also validated the involvement of these specific motifs containing regions of E1 by modeling elastic networks of E1. These motif involving interactions could be used as drug targets.

Keywords: E1, motifs, domains, INI1/hSNF5, replication protein A, p80/Uaf1 protein, histone H1, Hsp 40/70.

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[1]
Goodacre, N.; Devkota, P.; Bae, E.; Wuchty, S.; Uetz, P. Protein-protein interactions of human viruses. Semin. Cell Dev. Biol., 2020, 99, 31-39.
[http://dx.doi.org/10.1016/j.semcdb.2018.07.018] [PMID: 30031213]
[2]
Guven-Maiorov, E; Tsai, CJ; Nussinov, R Structural host-microbiota interaction networks. PLoS Computational Biology, 2017, 13(10), e1005579.
[http://dx.doi.org/10.1371/journal.pcbi.1005579]
[3]
Kurkcuoglu, O.; Kurkcuoglu, Z.; Doruker, P.; Jernigan, R.L. Collective dynamics of the ribosomal tunnel revealed by elastic network modeling. Proteins, 2009, 75(4), 837-845.
[http://dx.doi.org/10.1002/prot.22292] [PMID: 19004020]
[4]
Bauer, J.A.; Pavlović, J.; Bauerová-Hlinková, V. Normal mode analysis as a routine part of a structural investigation. Molecules, 2019, 24(18), 3293.
[http://dx.doi.org/10.3390/molecules24183293] [PMID: 31510014]
[5]
Kmiecik, S.; Kouza, M.; Badaczewska-Dawid, A.E.; Kloczkowski, A.; Kolinski, A. Modeling of protein structural flexibility and large-scale dynamics: coarse-grained simulations and elastic network models. Int. J. Mol. Sci., 2018, 19(11), 3496.
[http://dx.doi.org/10.3390/ijms19113496] [PMID: 30404229]
[6]
Hu, G.; Paola, L.D.; Liang, Z.; Giuliani, A. Comparative study of elastic network model and protein contact network for protein complexes: the hemoglobin case. BioMed Res. Int., 2017, 2017, 2483264.
[http://dx.doi.org/10.1155/2017/2483264]
[7]
Egawa, N.; Nakahara, T.; Ohno, S.; Narisawa-Saito, M.; Yugawa, T.; Fujita, M.; Yamato, K.; Natori, Y.; Kiyono, T. The E1 protein of human papillomavirus type 16 is dispensable for maintenance replication of the viral genome. J. Virol., 2012, 86(6), 3276-3283.
[http://dx.doi.org/10.1128/JVI.06450-11] [PMID: 22238312]
[8]
Dinkel, H.; Roey, V.K.; Michael, S.; Kumar, M.; Uyar, B.; Altenberg, B.; Milchevskaya, V.; Schneider, M.; Kühn, H.; Behrendt, A.; Dahl, S.L.; Damerell, V.; Diebel, S.; Kalman, S.; Klein, S.; Knudsen, A.C.; Mäder, C.; Merrill, S.; Staudt, A.; Thiel, V.; Welti, L.; Davey, N.E.; Diella, F.; Gibson, T.J. ELM 2016 - data update and new functionality of the eukaryotic linear motif resource. Nucleic Acids Res., 2016, 44(D1), D294-D300.
[http://dx.doi.org/10.1093/nar/gkv1291]
[9]
Pundir, S.; Martin, M.J.; O’Donovan, C. UniProt protein knowledgebase methods. Mol. Biol., 2017, 1558, 41-55.
[http://dx.doi.org/10.1007/978-1-4939-6783-4_2]
[10]
Ma, J.; Wang, S.; Zhao, F.; Xu, J. Protein threading using context-specific alignment potential. Bioinformatics (Proceedings of ISMB 2013), 2013, 29(13), pp. i257-i265.
[http://dx.doi.org/10.1093/bioinformatics/btt210]
[11]
Eyal, E.; Lum, G.; Bahar, I. The anisotropic network model web server at 2015 (ANM 2.0). Bioinformatics, 2015, 31(9), 1487-1489.
[http://dx.doi.org/10.1093/bioinformatics/btu847] [PMID: 25568280]
[12]
Atilgan, A.R.; Durell, S.R.; Jernigan, R.L.; Demirel, M.C.; Keskin, O.; Bahar, I. Anisotropy of fluctuation dynamics of proteins with an elastic network model. Biophys. J., 2001, 80(1), 505-515.
[http://dx.doi.org/10.1016/S0006-3495(01)76033-X] [PMID: 11159421]
[13]
Doruker, P.; Atilgan, A.R.; Bahar, I. Dynamics of proteins predicted by molecular dynamics simulations and analytical approaches: application to α-amylase inhibitor. Proteins, 2000, 40(3), 512-524.
[http://dx.doi.org/10.1002/1097-0134(20000815)40:3<512::AID-PROT180>3.0.CO;2-M] [PMID: 10861943]
[14]
Bergvall, M.; Melendy, T.; Archambault, J. The E1 proteins. Virology, 2013, 445(1-2), 35-56.
[http://dx.doi.org/10.1016/j.virol.2013.07.020] [PMID: 24029589]
[15]
Freitas, N.; Cunha, C. Mechanisms and signals for the nuclear import of proteins. Curr. Genomics, 2009, 10(8), 550-557.
[http://dx.doi.org/10.2174/138920209789503941] [PMID: 20514217]
[16]
Lehoux, M.; Fradet-Turcotte, A.; Lussier-Price, M.; Omichinski, J.G.; Archambault, J. Inhibition of human papillomavirus DNA replication by an E1-derived p80/UAF1-binding peptide. J. Virol., 2012, 86(7), 3486-3500.
[http://dx.doi.org/10.1128/JVI.07003-11] [PMID: 22278251]
[17]
Swindle, C.S.; Engler, J.A. Association of the human papillomavirus type 11 E1 protein with histone H1. J. Virol., 1998, 72(3), 1994-2001.
[http://dx.doi.org/10.1128/JVI.72.3.1994-2001.1998] [PMID: 9499053]
[18]
Lee, D.; Sohn, H.; Kalpana, G.V.; Choe, J. Interaction of E1 and hSNF5 proteins stimulates replication of human papillomavirus DNA. Nature, 1999, 399(6735), 487-491.
[http://dx.doi.org/10.1038/20966] [PMID: 10365963]
[19]
Sammak, S.; Allen, M.D.; Hamdani, N.; Bycroft, M.; Zinzalla, G. The structure of INI 1/hSNF 5 RPT 1 and its interactions with the c-MYC :MAX heterodimer provide insights into the interplay between MYC and the SWI/SNF chromatin remodeling complex. FEBS J., 2018, 285(22), 4165-4180.
[http://dx.doi.org/10.1111/febs.14660 ]
[20]
Yung, E.; Sorin, M.; Wang, E.J.; Perumal, S.; Ott, D.; Kalpana, G.V. Specificity of interaction of INI1/hSNF5 with retroviral integrases and its functional significance. J. Virol., 2004, 78(5), 2222-2231.
[http://dx.doi.org/10.1128/JVI.78.5.2222-2231.2004] [PMID: 14963118]
[21]
Lin, B.Y.; Makhov, A.M.; Griffith, J.D.; Broker, T.R.; Chow, L.T. Chaperone proteins abrogate inhibition of the human papillomavirus (HPV) E1 replicative helicase by the HPV E2 protein. Mol. Cell. Biol., 2002, 22(18), 6592-6604.
[http://dx.doi.org/10.1128/MCB.22.18.6592-6604.2002] [PMID: 12192057]
[22]
Loo, Y.M.; Melendy, T. Recruitment of replication protein A by the papillomavirus E1 protein and modulation by single-stranded DNA. J. Virol., 2004, 78(4), 1605-1615.
[http://dx.doi.org/10.1128/JVI.78.4.1605-1615.2004] [PMID: 14747526]

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