000276570 001__ 276570
000276570 005__ 20210129220914.0
000276570 0247_ $$2doi$$a10.1016/j.bpj.2015.06.040
000276570 0247_ $$2ISSN$$a0006-3495
000276570 0247_ $$2ISSN$$a1542-0086
000276570 0247_ $$2WOS$$aWOS:000362467100022
000276570 0247_ $$2altmetric$$aaltmetric:4610729
000276570 0247_ $$2pmid$$apmid:26445449
000276570 037__ $$aFZJ-2015-06935
000276570 082__ $$a570
000276570 1001_ $$0P:(DE-HGF)0$$aSólyom, Zsófia$$b0
000276570 245__ $$aThe Disordered Region of the HCV Protein NS5A: Conformational Dynamics, SH3 Binding, and Phosphorylation
000276570 260__ $$aCambridge, Mass.$$bCell Press$$c2015
000276570 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1449672681_32511
000276570 3367_ $$2DataCite$$aOutput Types/Journal article
000276570 3367_ $$00$$2EndNote$$aJournal Article
000276570 3367_ $$2BibTeX$$aARTICLE
000276570 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000276570 3367_ $$2DRIVER$$aarticle
000276570 520__ $$aIntrinsically disordered proteins (IDPs) perform their physiological role without possessing a well-defined threedimensional structure. Still, residual structure and conformational dynamics of IDPs are crucial for the mechanisms underlying their functions. For example, regions of transient secondary structure are often involved in molecular recognition, with the structure being stabilized (or not) upon binding. Long-range interactions, on the other hand, determine the hydrodynamic radius of the IDP, and thus the distance over which the protein can catch binding partners via so-called fly-casting mechanisms. The modulation of long-range interactions also presents a convenient way of fine-tuning the protein’s interaction network, by making binding sites more or less accessible. Here we studied, mainly by nuclear magnetic resonance spectroscopy, residual secondary structure and long-range interactions in nonstructural protein 5A (NS5A) from hepatitis C virus (HCV), a typical viral IDP with multiple functions during the viral life cycle. NS5A comprises an N-terminal folded domain, followed by a large (~250-residue) disordered C-terminal part. Comparing nuclear magnetic resonance spectra of full-length NS5A with those of a protein construct composed of only the C-terminal residues 191–447 (NS5A-D2D3) allowed us to conclude that there is no significant interaction between the globular and disordered parts of NS5A. NS5A-D2D3, despite its overall high flexibility, shows a large extent of local residual (a-helical and b-turn) structure, as well as a network of electrostatic long-range interactions. Furthermore, we could demonstrate that these long-range interactions become modulated upon binding to the host protein Bin1, as well as after NS5A phosphorylation by CK2. As the charged peptide regions involved in these interactions are well conserved among the different HCV genotypes, these transient long-range interactions may be important for some of the functions of NS5A over the course of the HCV life cycle.
000276570 536__ $$0G:(DE-HGF)POF3-553$$a553 - Physical Basis of Diseases (POF3-553)$$cPOF3-553$$fPOF III$$x0
000276570 588__ $$aDataset connected to CrossRef
000276570 7001_ $$0P:(DE-Juel1)132033$$aMa, Peixiang$$b1
000276570 7001_ $$0P:(DE-Juel1)132019$$aSchwarten, Melanie$$b2$$ufzj
000276570 7001_ $$0P:(DE-HGF)0$$aBosco, Michaël$$b3
000276570 7001_ $$0P:(DE-HGF)0$$aPolidori, Ange$$b4
000276570 7001_ $$0P:(DE-HGF)0$$aDurand, Grégory$$b5
000276570 7001_ $$0P:(DE-Juel1)132029$$aWillbold, Dieter$$b6$$ufzj
000276570 7001_ $$0P:(DE-HGF)0$$aBrutscher, Bernhard$$b7$$eCorresponding author
000276570 773__ $$0PERI:(DE-600)1477214-0$$a10.1016/j.bpj.2015.06.040$$gVol. 109, no. 7, p. 1483 - 1496$$n7$$p1483 - 1496$$tBiophysical journal$$v109$$x0006-3495$$y2015
000276570 8564_ $$uhttps://juser.fz-juelich.de/record/276570/files/The%20Disordered%20Region%20of%20the%20HCV%20Protein%20NS5A%3A%20Conformational%20Dynamics%2C%20SH3%20Binding%2C%20and%20Phosphorylation_2015.pdf$$yRestricted
000276570 8564_ $$uhttps://juser.fz-juelich.de/record/276570/files/The%20Disordered%20Region%20of%20the%20HCV%20Protein%20NS5A%3A%20Conformational%20Dynamics%2C%20SH3%20Binding%2C%20and%20Phosphorylation_2015.gif?subformat=icon$$xicon$$yRestricted
000276570 8564_ $$uhttps://juser.fz-juelich.de/record/276570/files/The%20Disordered%20Region%20of%20the%20HCV%20Protein%20NS5A%3A%20Conformational%20Dynamics%2C%20SH3%20Binding%2C%20and%20Phosphorylation_2015.jpg?subformat=icon-1440$$xicon-1440$$yRestricted
000276570 8564_ $$uhttps://juser.fz-juelich.de/record/276570/files/The%20Disordered%20Region%20of%20the%20HCV%20Protein%20NS5A%3A%20Conformational%20Dynamics%2C%20SH3%20Binding%2C%20and%20Phosphorylation_2015.jpg?subformat=icon-180$$xicon-180$$yRestricted
000276570 8564_ $$uhttps://juser.fz-juelich.de/record/276570/files/The%20Disordered%20Region%20of%20the%20HCV%20Protein%20NS5A%3A%20Conformational%20Dynamics%2C%20SH3%20Binding%2C%20and%20Phosphorylation_2015.jpg?subformat=icon-640$$xicon-640$$yRestricted
000276570 8564_ $$uhttps://juser.fz-juelich.de/record/276570/files/The%20Disordered%20Region%20of%20the%20HCV%20Protein%20NS5A%3A%20Conformational%20Dynamics%2C%20SH3%20Binding%2C%20and%20Phosphorylation_2015.pdf?subformat=pdfa$$xpdfa$$yRestricted
000276570 909CO $$ooai:juser.fz-juelich.de:276570$$pVDB
000276570 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)132019$$aForschungszentrum Jülich GmbH$$b2$$kFZJ
000276570 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)132029$$aForschungszentrum Jülich GmbH$$b6$$kFZJ
000276570 9131_ $$0G:(DE-HGF)POF3-553$$1G:(DE-HGF)POF3-550$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lBioSoft – Fundamentals for future Technologies in the fields of Soft Matter and Life Sciences$$vPhysical Basis of Diseases$$x0
000276570 9141_ $$y2015
000276570 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bBIOPHYS J : 2014
000276570 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000276570 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000276570 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000276570 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000276570 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000276570 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000276570 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000276570 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000276570 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000276570 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5
000276570 920__ $$lyes
000276570 9201_ $$0I:(DE-Juel1)ICS-6-20110106$$kICS-6$$lStrukturbiochemie $$x0
000276570 980__ $$ajournal
000276570 980__ $$aVDB
000276570 980__ $$aI:(DE-Juel1)ICS-6-20110106
000276570 980__ $$aUNRESTRICTED
000276570 981__ $$aI:(DE-Juel1)IBI-7-20200312