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Volume 13 Issue 12, December 2017

The cover depicts structures of dynamic and native conformational exchanger (DANCER) proteins, which were computationally designed to switch between predicted conformational states. DANCERs are based on the global fold of streptococcal protein Gβ1 and contain an engineered Trp43 residue that spontaneously exchanges between sequestered and solvent-exposed states on the millisecond timescale. Cover design by Erin Dewalt, based on an image from Adam Damry. Article, p1280

Research Highlights

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News & Views

  • The 'off-targets' of a drug are often poorly characterized yet could be harnessed in the treatment of complex diseases. A recent study used a small-molecule screening in non-small-cell lung cancer to repurpose an FDA-approved ALK/IGF1R inhibitor and uncover its mechanism of action.

    • Gaye Saginc
    • Franziska Voellmy
    • Rune Linding
    News & Views
  • Phage-assisted evolution can rapidly improve the efficiency and substrate specificity of orthogonal aminoacyl-tRNA synthetases. Furthermore, the crystal structure of the pyrrolysyl-tRNA synthetase N-terminal domain reveals the basis for these improvements and provides a structural rationale for orthogonality.

    • Jeffery M Tharp
    • Wenshe R Liu
    News & Views
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  • An inhibitor of the deubiquitinase (DUB) USP10 regulates the degradation of oncogenic FLT3, thus defining USP10 as a DUB for FLT3 and providing a therapeutic approach for human acute myeloid leukemia in which FLT3 activation is dysregulated.

    • Ellen L Weisberg
    • Nathan J Schauer
    • Sara J Buhrlage
  • A linear gating mechanism links kinetically and structurally distinct closed and open states of NMDA receptors. During allosteric inhibition, agonist binding incudes uncoupling of structural changes from gating motions in the first transmembrane region.

    • Drew M Dolino
    • Sudeshna Chatterjee
    • Vasanthi Jayaraman
  • A positive-selection CRISPR screen with the pro-oxidant paraquat (PQ) uncovers three genes mediating PQ-induced cell death: POR is the source of PQ-mediated reactive oxygen species (ROS) generation, and ATP7A and SLC45A4 promote oxidant-dependent cell death.

    • Colleen R Reczek
    • Kıvanç Birsoy
    • Navdeep S Chandel
  • The development of a computational protein design method, meta-multistate design, enables the design and validation of protein variants termed DANCERs that spontaneously exchange between predicted conformational states on the millisecond timescale.

    • James A Davey
    • Adam M Damry
    • Roberto A Chica
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