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@ARTICLE{Levorin:1042312,
      author       = {Levorin, Leonardo and Becker, Nina and Uluca-Yazgi, Boran
                      and Gardon, Luis and Kraus, Mirko and Sevenich, Marc and
                      Apostolidis, Athina and Schmitz, Kai and Rüter, Neomi and
                      Apanasenko, Irina and Willbold, Dieter and Hoyer, Wolfgang
                      and Neudecker, Philipp and Gremer, Lothar and Heise,
                      Henrike},
      title        = {{I}soleucine {S}ide {C}hains as {R}eporters of
                      {C}onformational {F}reedom in {P}rotein {F}olding {S}tudied
                      by {DNP}-{E}nhanced {NMR}},
      journal      = {Journal of the American Chemical Society},
      volume       = {147},
      number       = {18},
      issn         = {0002-7863},
      address      = {Washington, DC},
      publisher    = {ACS Publications},
      reportid     = {FZJ-2025-02519},
      pages        = {15867 - 15879},
      year         = {2025},
      abstract     = {Conformations of protein side chains are closely linked to
                      protein function. DNP-enhanced solid-state NMR (ssNMR),
                      which operates at cryogenic temperatures (<110 K), can be
                      used to freeze-trap protein conformations, including the
                      side chains. In the present study, we employed
                      two-dimensional DNP-enhanced ssNMR to get detailed insights
                      into backbone and side chain conformations of isoleucine. We
                      used different amino acid selectively labeled model proteins
                      for intrinsically disordered proteins (IDPs), denatured and
                      well-folded proteins, and amyloid fibrils. 13C chemical
                      shifts are closely correlated with secondary structure
                      elements and χ1 and χ2 angles in isoleucine side chains.
                      Thus, line shape analysis by integration of representative
                      peak areas in 2D spectra provides an accurate overview of
                      the distribution of backbone and side chain conformations.
                      For the well-folded proteins GABARAP and bovine PI3-kinase
                      (PI3K) SH3 domain, most Ile chemical shifts in frozen
                      solution are well resolved and similar to those observed in
                      solution. However, line widths of individual Ile residues
                      are directly linked to residual mobility, and line
                      broadening or even signal splitting appears for those Ile
                      residues, which are not part of well-defined secondary
                      structure elements. For unfolded PI3K SH3 and the IDP
                      α-synuclein (α-syn), all Ile side chains have full
                      conformational freedom, and as a consequence, inhomogeneous
                      line broadening dominates the cryogenic spectra. Moreover,
                      we demonstrate that conformational ensembles of proteins
                      strongly depend on solvent and buffer conditions. This
                      allowed different unfolded structures for chemical and
                      acidic pH denaturation of the PI3K SH3 domain to be
                      distinguished. In amyloid fibrils of α-syn and PI3K SH3,
                      chemical shifts typical for β-strand like secondary
                      structure dominate the spectra, whereas Ile residues
                      belonging to the fuzzy coat still add the IDP-type line
                      shapes. Hence, DNP-enhanced ssNMR is a useful tool for
                      investigating side chain facilitated protein functions and
                      interactions.},
      cin          = {IBI-7},
      ddc          = {540},
      cid          = {I:(DE-Juel1)IBI-7-20200312},
      pnm          = {5244 - Information Processing in Neuronal Networks
                      (POF4-524)},
      pid          = {G:(DE-HGF)POF4-5244},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {40285725},
      UT           = {WOS:001477553300001},
      doi          = {10.1021/jacs.5c04159},
      url          = {https://juser.fz-juelich.de/record/1042312},
}