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@ARTICLE{Yerabham:830257,
      author       = {Yerabham, ASK and Mas, PJ and Decker, Christina and Soares,
                      DC and Weiergräber, Oliver H. and Nagel-Steger, Luitgard
                      and Willbold, Dieter and Hart, DJ and Bradshaw, NJ and
                      Korth, C.},
      title        = {{A} structural organization for the {D}isrupted in
                      {S}chizophrenia 1 protein, identified by high-throughput
                      screening, reveals distinctly folded regions, which are
                      bisected by mental illness-related mutations},
      journal      = {The journal of biological chemistry},
      volume       = {292},
      issn         = {0021-9258},
      address      = {Bethesda, Md.},
      publisher    = {Soc.},
      reportid     = {FZJ-2017-03830},
      pages        = {6468–6477},
      year         = {2017},
      abstract     = {Disrupted in Schizophrenia 1 (DISC1) is a scaffolding
                      protein of significant importance for neurodevelopment and a
                      prominent candidate protein in the pathology of major mental
                      illness. DISC1 modulates a number of critical neuronal
                      signaling pathways through protein-protein interactions;
                      however, the mechanism by which this occurs and how DISC1
                      causes mental illness is unclear, partly because knowledge
                      of the structure of DISC1 is lacking. A lack of homology
                      with known proteins has hindered attempts to define its
                      domain composition. Here, we employed the high-throughput
                      Expression of Soluble Proteins by Random Incremental
                      Truncation (ESPRIT) technique to identify discretely folded
                      regions of human DISC1 via solubility assessment of tens of
                      thousands of fragments of recombinant DISC1. We identified
                      four novel structured regions, named D, I, S, and C, at
                      amino acids 257–383, 539–655, 635–738, and 691–836,
                      respectively. One region (D) is located in a DISC1 section
                      previously predicted to be unstructured. All regions
                      encompass coiled-coil or α-helical structures, and three
                      are involved in DISC1 oligomerization. Crucially, three of
                      these domains would be lost or disrupted by a chromosomal
                      translocation event after amino acid 597, which has been
                      strongly linked to major mental illness. Furthermore, we
                      observed that a known illness-related frameshift mutation
                      after amino acid 807 causes the C region to form aberrantly
                      multimeric and aggregated complexes with an unstable
                      secondary structure. This newly revealed domain architecture
                      of DISC1, therefore, provides a powerful framework for
                      understanding the critical role of this protein in a variety
                      of devastating mental illnesses.},
      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:000399813400005},
      pubmed       = {pmid:28249940},
      doi          = {10.1074/jbc.M116.773903},
      url          = {https://juser.fz-juelich.de/record/830257},
}