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@ARTICLE{Slyom:276570,
      author       = {Sólyom, Zsófia and Ma, Peixiang and Schwarten, Melanie
                      and Bosco, Michaël and Polidori, Ange and Durand, Grégory
                      and Willbold, Dieter and Brutscher, Bernhard},
      title        = {{T}he {D}isordered {R}egion of the {HCV} {P}rotein
                      {NS}5{A}: {C}onformational {D}ynamics, {SH}3 {B}inding, and
                      {P}hosphorylation},
      journal      = {Biophysical journal},
      volume       = {109},
      number       = {7},
      issn         = {0006-3495},
      address      = {Cambridge, Mass.},
      publisher    = {Cell Press},
      reportid     = {FZJ-2015-06935},
      pages        = {1483 - 1496},
      year         = {2015},
      abstract     = {Intrinsically 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.},
      cin          = {ICS-6},
      ddc          = {570},
      cid          = {I:(DE-Juel1)ICS-6-20110106},
      pnm          = {553 - Physical Basis of Diseases (POF3-553)},
      pid          = {G:(DE-HGF)POF3-553},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:000362467100022},
      pubmed       = {pmid:26445449},
      doi          = {10.1016/j.bpj.2015.06.040},
      url          = {https://juser.fz-juelich.de/record/276570},
}