Role of ORF4 in Hepatitis E virus regulation: analysis of intrinsically disordered regions

Alves C, Cheng H, Roder H, Taylor J (2010) Intrinsic disorder and oligomerization of the hepatitis delta virus antigen. Virology 407(2):333–340

Ansari IH, Nanda SK, Durgapal H, Agrawal S, Mohanty SK, Gupta D, Jameel S, Panda SK (2000) Cloning, sequencing, and expression of the hepatitis E virus (HEV) nonstructural open reading frame 1 (ORF1). J Med Virol 60(3):275–283

Best SM, Morris KL, Shannon JG, Robertson SJ, Mitzel DN, Park GS, Boer E, Wolfinbarger JB, Bloom ME (2005) Inhibition of interferon-stimulated JAK-STAT signaling by a tick-borne flavivirus and identification of NS5 as an interferon antagonist. J Virol 79(20):12828–12839

Betts MJ, Russell RB (2003) Amino acid properties and consequences of substitutions. Bioinform Genet 317(289):10–12

Bhatnagar G, Sharma S, Kumar A, Prasad S, Agarwal S, Kar P (2016) Reduced glutathione in hepatitis E infection and pregnancy outcome. J Obstet Gynaecol Res 42(7):789–795

Bhattacharya D, Mayuri BSM, Perera R, Kuhn RJ, Striker R (2009) Protein Kinase G phosphorylates mosquito-borne flavivirus NS5. J Virol 83(18):9195–9205

Boccia D, Guthmann JP, Klovstad H, Hamid N, Tatay M, Ciglenecki I, Nizou JY, Nicand E, Guerin PJ (2006) High mortality associated with an outbreak of hepatitis E among displaced persons in Darfur. Sudan Clin Infect Dis 42(12):1679–1684

Campen A, Williams RM, Brown CJ, Meng J, Uversky VN, Dunker AK (2008a) TOP-IDP-scale: a new amino acid scale measuring propensity for intrinsic disorder. Protein Pept Lett 15:956–963

Campen A, Williams RM, Brown CJ, Meng J, Uversky VN, Dunker AK (2008b) TOP-IDP-scale: a new amino acid scale measuring propensity for intrinsic disorder. Protein Pept Lett 15(9):956–963

Chandra V, Taneja S, Kalia M, Jameel S (2008) Molecular biology and pathogenesis of hepatitis E virus. J Biosci 33(4):451–464

Collins MO, Yu L, Campuzano I, Grant SG, Choudhary JS (2008) Phosphoproteomic analysis of the mouse brain cytosol reveals a predominance of protein phosphorylation in regions of intrinsic sequence disorder. Mol Cell Proteom 7(7):1331–1348

Dafforn TR, Smith CJ (2004) Natively unfolded domains in endocytosis: hooks, lines and linkers. EMBO Rep 5(11):1046–1052

Dé I, Fata-Hartley C, Sawicki SG, Sawicki DL (2003) Functional analysis of nsP3 phosphoprotein mutants of Sindbis virus. J Virol 77(24):13106–13116

De Chassey B, Navratil V, Tafforeau L (2008) Hepatitis C virus infection protein network. Mol Syst Biol 4(1):230

Denning DP, Rexach MF (2007) Rapid Evolution Exposes the Boundaries of Domain Structure and Function in Natively Unfolded FG Nucleoporins* S. Mol Cell Proteom 6(2):272–282

Diella F, Haslam N, Chica C, Budd A, Michael S, Brown NP, Travé G, Gibson TJ (2008) Understanding eukaryotic linear motifs and their role in cell signaling and regulation. J Front Biosci 13(6580):603

Ding Q, Heller B, Capuccino JM, Song B, Nimgaonkar I, Hrebikova G, Contreras JE, Ploss A (2017) Hepatitis E virus ORF3 is a functional ion channel required for release of infectious particles. Proc Natl Acad Sci USA 114(5):1147–1152

Disfani FM, Hsu W-L, Mizianty MJ et al (2012) MoRFpred, a computational tool for sequence-based prediction and characterization of short disorder-to-order transitioning binding regions in proteins. Bioinformatics 28(12):i75–i83

Dosztanyi Z, Chen J, Dunker K, Simon I, Tompa P (2006) Disorder and sequence repeats in hub proteins and their implications for network evolution. J Proteome Res 5(11):2985–2995

Dunker AK, Obradovic Z (2001) The protein trinity—linking function and disorder. Nat Biotechnol 19:805–806

Dunker AK, Garner E, Guilliot S, Romero P, Albrecht K, Hart J, Obradovic Z, Kissinger C, Villafranca JE (1998) Protein disorder and the evolution of molecular recognition: theory, predictions and observations. Pac Symp Biocomput 1998:473–484

Dunker AK, Lawson JD, Brown CJ, Williams RM, Romero P, Oh JS, Oldfield CJ, Campen AM, Ratliff CM, Hipps KW, Aussio J, Nissen MS, Reeves R, Kang C, Kissinger CR, Bailey RW, Griswold MD, Chiu W, Garner EC, Obradovic Z (2001a) Intrinsically disordered protein. J Mol Graph Model 19:26–59

Dunker AK, Lawson JD, Brown CJ, Williams RM, Romero P, Oh JS, Oldfield CJ, Campen AM, Ratliff CM, Hipps KW, Ausio J (2001b) Intrinsically disordered protein. J Mol Graph Model 19:26–59

Dunker AK, Lawson JD, Brown CJ (2001c) Intrinsically disordered protein. J Mol Graph Model 3263:26–59

Dunker AK, Brown CJ, Lawson JD, Iakoucheva LM, Obradovic Z (2002a) Intrinsic disorder and protein function. Biochemistry 41:6573–6582

Dunker AK, Brown CJ, Obradovic Z (2002b) Identification and functions of usefully disordered proteins. Adv Protein Chem 62:25–49

Dunker AK, Oldfield CJ, Meng J, Romero P, Yang JY, Chen JW, Vacic V, Obradovic Z, Uversky VN (2008) The unfoldomics decade: an update on intrinsically disordered proteins. BMC Genom 9(2):1–26

Dyson HJ, Wright PE (1998) Equilibrium NMR studies of unfolded and partially folded proteins. Nat Struct Biol 5(7):499–503

Dyson HJ, Wright PE (2002) Coupling of folding and binding for unstructured proteins. Curr Opin Struct Biol 12:54–60

Dyson HJ, Wright PE (2005) Intrinsically unstructured proteins and their functions. Nat Rev Mol Cell Biol 6:197–208

Edwards YJ, Lobley AE, Pentony MM, Jones DT (2009) Insights into the regulation of intrinsically disordered proteins in the human proteome by analyzing sequence and gene expression data. Genome Biol 10(5):1–8

Erdős G, Dosztányi Z (2020) Analyzing protein disorder with IUPred2A. Curr Protoc Bioinform 70(1):e99

Espinoza-Fonseca LM (2009) Thermodynamic aspects of coupled binding and folding of an intrinsically disordered protein: a computational alanine scanning study. Biochemistry 48(48):11332–11334

Fischer E (1894) Einfluss der configuration auf die wirkung der enzyme. Ber Dt Chem Ges 27:2985–2993

Forwood JK, Brooks A, Briggs LJ, Xiao CY, Jans DA, Vasudevan SG (1999) The 37-amino-acid interdomain of Dengue Virus NS5 Protein Contains a Functional NLS and Inhibitory CK2 Site. Biochem Biophys Res Commun 257(3):731–737

Foster TL, Belyaeva T, Stonehouse NJ, Pearson AR, Harris M (2010) All three domains of the hepatitis C virus nonstructural NS5A protein contribute to RNA binding. J Virol 84:9267–9277

Foy NJ, Akhrymuk M, Akhrymuk I, Atasheva S, Bopda-Waffo A, Frolov I, Frolova EI (2013) Hypervariable domains of nsP3 proteins of New World and Old World alphaviruses mediate formation of distinct, virus-specific protein complexes. J Virol 87(4):1997–2010

Galea CA, Wang Y, Sivakolundu SG, Kriwacki RW (2008) Regulation of cell division by intrinsically unstructured proteins: intrinsic flexibility, modularity, and signaling conduits. Biochemistry 47(29):7598–7609

Garner E, Cannon P, Romero P, Obradovic Z, Dunker AK (1998) Predicting disordered regions from amino acid sequence: common themes despite differing structural characterization. Genome Inform Ser Workshop Genome Inform 9:201–213

Gerard FCA, Ribeiro EdA, Leyrat C (2009) Modular organization of rabies virus phosphoprotein. J Mol Biol 388:978–996

Gianni S, Dogan J, Jemth P (2016) Coupled binding and folding of intrinsically disordered proteins: what can we learn from kinetics? Curr Opin Struct Biol 36:18–24

Giri R, Kumar D, Sharma N, Uversky VN (2016) Intrinsically disordered side of the Zika virus proteome. Front Cell Infect Microbiol 6:144

Grainger L, Cicchini L, Rak M, Petrucelli A, Fitzgerald KD, Semler BL, Goodrum F (2010) Stress- inducible alternative translation initiation of human cytomegalovirus latency protein pUL138. J Virol 84(18):9472–9486

Gsponer J, Futschik ME, Teichmann SA, Babu MM (2008) Tight regulation of unstructured proteins: from transcript synthesis to protein degradation. Science 322:1365–1368

Habchi J, Longhi S (2012) Structural disorder within paramyxovirus nucleoproteins and phosphoproteins. Mol Biosyst 8:69–81

He M, Wang M, Huang Y, Peng W, Zheng Z, Xia N, Xu J, Tian D (2016) The ORF3 protein of genotype 1 hepatitis E virus suppresses TLR3-induced NF-κB signaling via TRADD and RIP1. Sci Rep 6(1):1–13

Holt LJ, Tuch BB, Villén J, Johnson AD, Gygi SP, Morgan DO (2009) Global analysis of Cdk1 substrate phosphorylation sites provides insights into evolution. Science 325(5948):1682–1686

Iakoucheva LM, Radivojac P, Brown CJ. Oconnor TR, Sikes JG, Obradovic Z, Dunker AK (2004) Nucleic Acids Res 32:1037–1049

Iwasaki M, Takeda M, Shirogane Y, Nakatsu Y, Nakamura T, Yanagi Y (2009) The matrix protein of measles virus regulates viral RNA synthesis and assembly by interacting with the nucleocapsid protein. J Virol 83:10374–10383

Jones DT, Cozzetto D (2015) DISOPRED3: precise disordered region predictions with annotated protein-binding activity. Bioinformatics 31(6):857–863

Joseph AP, Srinivasan N, de Brevern AG (2012) Cis-trans peptide variations instructurally similar proteins. Amino Acids 43:1369–1381

Kalhan SC, Hanson RW (2012) Resurgence of serine: an often neglected but indispensable amino acid. J Biol Chem 287(24):19786–19791

Kamar N, Selves J, Mansuy JM, Ouezzani L, Péron JM, Guitard J, Cointault O, Esposito L, Abravanel F, Danjoux M, Durand D (2008) Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med 358(8):811–817

Kamar N, Izopet J, Pavio N, Aggarwal R, Labrique A, Wedemeyer H, Dalton HR (2017) Hepatitis E virus infection. Nat Rev Dis Primers 3(1):1–6

Kapoor M, Zhang L, Ramachandra M, Kusukawa J, Ebner KE, Padmanabhan R (1995) Association between NS3 and NS5 proteins of dengue virus Type 2 in the Putative RNA replicase is linked to differential phosphorylation of NS5. J Biol Chem 270(32):19100–19106

Karlin D, Longhi S, Receveur V, Canard B (2002) The n-terminal domain of the phosphoprotein of morbilliviruses belongs to the natively unfolded class of proteins. Virology 296:251–262

Karlin D, Ferron F, Canard B, Longhi S (2003) Structural disorder and modular organization in Paramyxovirinae N and P. J Gen Virol 84:3239–3252

Karush F (1950) Heterogeneity of the binding sites of bovine serum albumin1. J Am Chem Soc 72:2705–2713

Kriwacki RW, Hengst L, Tennant L, Reed SI, Wright PE (1996) Structural studies of p21Waf1/Cip1/Sdi1 in the free and Cdk2-bound state: conformational disorder mediates binding diversity. Proc Natl Acad Sci USA 93:11504–11509

Kumar M, Gromiha MM, Raghava GPS (2008) Prediction of RNA binding sites in a protein using SVM and PSSM profle. Proteins 71(1):189–194

Landry CR, Levy ED, Michnick SW (2009) Weak functional constraints on phosphoproteomes. Trends Genet 25(5):193–197

Lee SH, Kim DH, Han J, Cha EJ, Lim JE, Cho YJ, Lee C, Han KH (2012) Understanding pre-structured motifs (PreSMos) in intrinsically unfolded proteins. Curr Protein Pept Sci 13(1):34–54

Leyrat C, Jensen MR, Ribeiro EA (2011) The N0-binding region of the vesicular stomatitis virus phosphoprotein is globally disordered but contains transient α-helices. Protein Sci 20:542–556

Lhomme S, Marion O, Abravanel F, Chapuy-Regaud S, Kamar N, Izopet J (2016) Hepatitis E pathogenesis. Viruses 8(8):212

Li G, La Starza MW, Hardy WR, Strauss JH, Rice CM (1990) Phosphorylation of Sindbis virus nsP3 in vivo and in vitro. Virology 179(1):416–427

Lin RJ, Chang BL, Yu HP, Liao CL, Lin YL (2006) Blocking of interferon-induced Jak-Stat signaling by Japanese encephalitis virus NS5 through a protein tyrosine phosphatase-mediated mechanism. J Virol 80(12):5908–5918

Llorente MT, García-Barreno B, Calero M (2006) Structural analysis of the human respiratory syncytial virus phosphoprotein: characterization of an α-helical domain involved in oligomerization. J Gen Virol 87:159–169

Macdonald A, Harris M (2004) Hepatitis C virus NS5A: tales of a promiscuous protein. J Gen Virol 85:2485–2502

Mann M, Ong SE, Grønborg M, Steen H, Jensen ON, Pandey A (2002) Analysis of protein phosphorylation using mass spectrometry: deciphering the phosphoproteome. Trends Biotechnol 20(6):261–268

Marks F (1996) Protein phosphorylation. VCH Weinheim, New York, Basel, Cambridge, Tokyo

Meruelo AD, Han SK, Kim S, Bowie JU (2012) Structural differences between thermophilic and mesophilic membrane proteins. Protein Sci 21:1746–1753

Mészáros B, Erdős G, Dosztányi Z (2018) IUPred2A: context-dependent prediction of protein disorder as a function of redox state and protein binding. Nucleic Acids Res 46(W1):W329–W337

Mishra PM, Verma NC, Rao C, Uversky VN, Nandi CK (2020) Intrinsically disordered proteins of viruses: Involvement in the mechanism of cell regulation and pathogenesis. Prog Mol Biol Transl Sci 174:1

Mohan A, Oldfield CJ, Radivojac P, Vacic V, Cortese MS, Dunker AK, Uversky VN (2006) Analysis of molecular recognition features (MoRFs). J Mol Biol 362(5):1043–1059

Mori Y, Matsuura Y (2011) Structure of hepatitis E viral particle. Virus Res 161(1):59–64

Nair VP, Anang S, Subramani C, Madhvi A, Bakshi K, Srivastava A, Nayak B, Ranjith Kumar CT, Surjit M (2016) Endoplasmic reticulum stress induced synthesis of a novel viral factor mediates efficient replication of Genotype-1 Hepa-titis E virus. PLoS Pathog 12(4):05521

Necci M, Piovesan D, Tosatto SCE (2016) Large-scale analysis of intrinsic disorder flavors and associated functions in the protein sequence universe. Protein Sci 25:2164–2174

Oldfeld CJ, Dunker AK (2014) Intrinsically disordered proteins and intrinsically disordered protein regions. Annu Rev Biochem 83:553–584. https://doi.org/10.1146/annurev-biochem-072711-164947

Parvez MK (2013) Molecular characterization of hepatitis E virus ORF1 gene supports apapain-like cysteine protease (PCP)- domain activity. Virus Res 178(2):553–556

Parvez MK, Al-Dosari MS (2015) Evidence of MAPK-JNK1/2 activation by hepatitis E virus ORF3 protein in cultured hepatoma cells. Cytotechnology 67(3):545–550

Peng ZKL (2015) High-throughput prediction of RNA, DNA and protein binding regions mediated by intrinsic disorder. Nucleic Acids Res 43:e121

Peng K, Vucetic S, Radivojac P, Brown CJ, Dunker AK, Obradovic Z (2005) Optimizing long intrinsic disorder predictors with protein evolutionary information. J Bioinform Comput Biol 3(01):35–60

Peng K, Radivojac P, Vucetic S, Dunker AK, Obradovic Z (2006) Length-dependent prediction of protein intrinsic disorder. BMC Bioinform 7(1):1–17

Peng Z, Wang C, Uversky VN, Kurgan L (2017) Prediction of disordered RNA, DNA, and protein binding regions using DisoRDPbind. Methods Mol Biol 1484:187–203

Pérez-Gracia MT, Suay-García B, Mateos-Lindemann ML (2017) Hepatitis E and pregnancy: Current state. Rev Med Virol 27(3):e1929

Purdy MA, Lara J, Khudyakov YE (2012) The hepatitis E virus polyproline region is involved in viral adaptation. PLoS ONE 7(4):e35974

Radivojac P, Vacic V, Haynes C, Cocklin RR, Mohan A, Heyen JW, Goebl MG, Iakoucheva LM (2010) Identification, analysis and prediction of protein ubiquitination sites. Proteins Struct Funct Bioinform 78(2):365–380

Rajagopal KA, Indira, Tan T (2021) Structure & function–amino acids. https://bio.libretexts.org/@go/page/7809

Ramakrishnan C, Ramachandran GN (1965) Stereochemical criteria for polypeptide and protein chain conformations. II. Allowed conformations for a pair of peptide units. Biophys J 5:909–933

Rizzetto M (2009) Hepatitis D: thirty years after. J Hepatol 50(5):1043–1050

Romero P, Obradovic Z, Li X et al (2001a) Sequence complexity of disordered protein. Proteins Struct Funct Genet 42(1):38–48

Romero P, Obradovic Z, Li X, Garner EC, Brown CJ, Dunker AK (2001b) Sequence complexity of disordered protein. Proteins 42:38–48

Roy A, Xu D, Poisson J, Zhang Y (2011) A protocol for computer-based protein structure and function prediction. J Vis Exp;e3259

Roy A, Zhang Y (2011) Recognizing protein-ligand binding sites by global structural alignment and local geometry refinement. Structure 20(6):987–997

Schweiger R, Linial M (2010) Cooperativity within proximal phosphorylation sites is revealed from large-scale proteomics data. Biol Direct 5(1):1–7

Shrestha A, Adhikari A, Bhattarai M, Rauniyar R, Debes JD, Boonstra A, Lama TK, Al Mahtab M, Butt AS, Akbar SM, Aryal N (2017) Prevalence and risk of hepatitis E virus infection in the HIV population of Nepal. Virol J 14(1):1–7

Singh A, Kumar A, Yadav R et al (2018) Deciphering the dark proteome of Chikungunya virus. Sci Rep 8:5822

Subramani C, Nair VP, Anang S, Mandal SD, Pareek M, Kaushik N, Srivastava A, Saha S, Nayak B, Ranjith-Kumar CT, Surjit M (2018) Host-virus protein interaction network reveals the involvement of multiple host processes in the life cycle of hepatitis E Virus. Msystems 3(1):e00135

Tam AW, Smith MM, Guerra ME, Huang CC, Bradley DW, Fry KE, Reyes GR (1991) Hepatitis E virus (HEV): molecular cloning and sequencing of the full-length viral genome. Virology 185(1):120–131

Tavitian S, Peron JM, Huguet F, Kamar N, Abravanel F, Beyne-Rauzy O, Oberic L, Faguer S, Alric L, Roussel M, Gaudin C (2015) Ribavirin for chronic hepatitis prevention among patients with hematologic malignancies. Emerg Infect Dis 21(8):1466

Tompa P (2002) Intrinsically unstructured proteins. Trends Biochem Sci 27:527–533

Uversky VN (2002) Natively unfolded proteins: a point where biology waits for physics. Protein Sci 11:739–756

Uversky VN (2011) Intrinsically disordered proteins from A to Z. Int J Biochem Cell Biol 43:1090–1103

Uversky VN (2013) Unusual biophysics of intrinsically disordered proteins. Biochim Biophys Acta Proteins Proteom 1834(5):932–951

Vacic V, Uversky VN, Dunker AK, Lonardi S (2007) Composition Profiler: a tool for discovery and visualization of amino acid composition differences. BMC Bioinform 8:211

Van Der Lee R, Buljan M, Lang B et al (2014a) Classifcation of intrinsically disordered regions and proteins. Chem Rev 114:6589–6631

Van Der Lee R, Buljan M, Lang B, Weatheritt RJ, Daughdrill GW, Dunker AK, Fuxreiter M, Gough J, Gsponer J, Jones DT, Kim PM (2014c) Classifcation of intrinsically disordered regions and proteins. Chem Rev 114:6589–6631

Van der Lee R, Lang B, Kruse K, Gsponer J, de Groot NS, Huynen MA, Matouschek A, Fuxreiter M, Babu MM (2014b) Intrinsically disordered segments affect protein half-life in the cell and during evolution. Cell Rep 8:18

Verdegem D, Badillo A, Wieruszeski JM (2011) Domain 3 of NS5A protein from the hepatitis C virus has intrinsic α-helical propensity and is a substrate of cyclophilin A. J Biol Chem 286:20441–20454

Vihinen H, Ahola T, Tuittila M, Merits A, Kääriäinen L (2001) Elimination of phosphorylation sites of Semliki Forest virus replicase protein nsP3. J Biol Chem 276(8):5745–5752

Wang J, Cao Z, Zhao L, Li S (2011) Novel strategies for drug discovery based on intrinsically disordered proteins (IDPs). Int J Mol Sci 12(5):3205–3219

Ward JJ, Sodhi JS, McGufn LJ et al (2004a) Prediction and functional analysis of native disorder in proteins from the three kingdoms of life. J Mol Biol 337:635–645

Ward JJ, McGuffin LJ, Bryson K, Buxton BF, Jones DT (2004b) The DISOPRED server for the prediction of protein disorder. Bioinformatics 20:2138–2139

Williams RM, Obradovic Z, Mathura V, Braun W, Garner EC, Young J, Takayama S, Brown CJ, Dunker AK (2001) The protein non-folding problem: amino acid determinants of intrinsic order and disorder. Pac Symp Biocomput 2001:89–100

Wright PE, Dyson HJ (1999) Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm. J Mol Biol 293:321–331

Wright PE, Dyson HJ (2009) Linking folding and binding. Curr Opin Struct Biol 19(1):31–38

Wright PE, Dyson HJ (2015) Intrinsically disordered proteins in cellular signalling and regulation. Nat Rev Mol Cell Biol 16(1):18–29

Xue B, Williams RW, Oldfield CJ, Goh GK, Dunker AK, Uversky VN (2010) Viral disorder or disordered viruses: do viral proteins possess unique features? Protein Pept Lett 17:932–951

Xue B, Blocquel D, Habchi J (2014) Structural disorder in viral proteins. Chem Rev 114:6880–6911

Yan J, Kurgan L (2017a) DRNApred, fast sequence-based method that accurately predicts and discriminates DNA- and RNA-binding residues. Nucleic Acids Res 45(10):e84

Yan J, Kurgan L (2017b) DRNApred, fast sequence-based method that accurately predicts and discriminates DNA- and RNA-binding residues. Nucleic Acids Res 45(10):e84–e84

Zor T, Mayr BM, Dyson HJ, Montminy MR, Wright PE (2002) Roles of phosphorylation and helix propensity in the binding of the KIX domain of CREB-binding protein by constitutive (c-Myb) and inducible (CREB) activators. J Biol Chem 277(44):42241–42248