News & Views in 2019

Filter By:

Article Type
Year
  • Microbially derived peptides that mimic immunogenic gliadin peptides in celiac disease have been identified using a structure- and sequence-guided search. T cell activation assays and crystal structures reveal that a protein from the commensal bacterium Pseudomonas fluorescens can be processed and presented by antigen-presenting cells to potently activate T cells from patients with celiac disease.

    • Elena F. Verdu
    • Detlef Schuppan
    News & Views
  • A study reports the structures of membrane-bound flavin-containing monooxygenases (FMOs), solved using reconstructed ancestral mammalian FMOs. The models provide a structural basis for these enzymes’ mechanism of action and show how the proteins interact with membranes and how substrates access their active sites.

    • Ian R. Phillips
    • Elizabeth A. Shephard
    News & Views
  • Bacterial T-boxes are regulatory mRNA regions that control the transcription or translation of factors involved in amino acid supply. T-boxes act by directly binding to non-aminoacylated tRNA in response to amino acid starvation. Three studies now capture three-dimensional structures of tRNA–T-box complexes and reveal a set of RNA features that are required for the recognition of specific tRNAs and modulation of gene expression.

    • Jacob W. Weaver
    • Alexander Serganov
    News & Views
  • Stabilization of the 3D genome architecture surrounding DNA lesions is critical for the maintenance of genome integrity. A new report by Ochs et al. shows how 53BP1 and RIF1 assemble a higher-order structure in the vicinity of damaged chromatin to protect it from unscheduled DNA-end resection.

    • Indrajeet Ghodke
    • Evi Soutoglou
    News & Views
  • Finally, the architecture of the translocase of the mitochondrial outer membrane (TOM complex) is revealed, after 20 years of anticipation. Two groups have now determined the near-atomic structures of the TOM complex. These findings improve understanding of the mechanisms by which TOM facilitates the passage of about 1,000 different proteins from the cytosol into the mitochondria.

    • Doron Rapaport
    News & Views
  • Segmented, double-stranded RNA viruses of the Reoviridae family tightly regulate the activity of encapsidated polymerases to mediate the transition between genome replication and iterative rounds of multipartite transcription within a particle. By resolving multiple in situ structures of the transcribing complex, a new study reveals enzyme conformational changes and RNA trajectories during specific transcriptional states that support an ‘ouroboros’ model of conservative transcription for a member of the Reoviridae family.

    • Kristen Ogden
    News & Views
  • Chromatin is compartmentalized spatially and temporally at multiple levels, but the precise organization of chromatin and mechanisms underlying its restructuring remain unclear. Two studies published in Cell and Nature now demonstrate the ability of chromatin to undergo liquid–liquid phase separation under physiological conditions and show that this intrinsic physicochemical property of chromatin can be regulated.

    • Yi Zhang
    • Tatiana G. Kutateladze
    News & Views
  • Upregulation of the X chromosome compensates for the presence of a single active X chromosome in mammals, but this has been difficult to measure and to understand mechanistically. A study now demonstrates that increased burst frequency boosts the transcriptional output of X-linked genes in male and female cells with a single active X chromosome. Interestingly, female embryonic stem cells lack increased burst frequency, which is established only after inactivation of the X chromosome takes place; this finding reveals a switch that can modulate transcriptional bursting.

    • Xinxian Deng
    • Christine M. Disteche
    News & Views
  • A new cryo-EM structure of the bacterial flagellar hook, which connects the motor to the flagellar filament, reveals 11 distinctive conformations of the subunit. The cooperative dynamic switching among these states offers a dramatic extension of two-state models of protein allostery.

    • Edward H. Egelman
    News & Views
  • Beige fat serves as a substantial metabolic sink that dissipates energy and has consequently attracted much attention as a target for improving metabolic health. A recent study has provided a new molecular target, the N-terminal acetyltransferase Naa10p, for harnessing beige-fat biogenesis and improving whole-body energy homeostasis1.

    • Qiang Wang
    • Shingo Kajimura
    News & Views
  • The ‘N-end rule’ correlates the identity of the N-terminal residue of a protein to its in vivo half-life. A study has now shown that an N-terminal glycine can serve as a potent degradation signal, which reveals a novel branch of N terminus–dependent protein degradation.

    • Mohamed Eldeeb
    • Mansoore Esmaili
    • Richard Fahlman
    News & Views
  • Small RNAs guide nuclear Argonaute proteins to silence genomic target loci via recruitment of factors that lead to formation of repressive heterochromatin. Animal gonads use this pathway to repress transposable elements with PIWI-clade Argonaute proteins and their associated small RNAs called PIWI-interacting RNAs (piRNAs). Four research groups now identify a protein complex that acts as a molecular bridge between the piRNA pathway and the epigenetic silencing machinery.

    • David Homolka
    • Ramesh S. Pillai
    News & Views
  • Researchers have sought to understand the function and regulation of the motor protein dynein since its discovery more than 50 years ago1. Dynein-2 is one of the motors that move the intraflagellar transport (IFT) trains ― large protein complexes that are needed for the assembly and function of eukaryotic cilia and flagella. Toropova et al. report the single-particle cryo-EM structure of the human dynein-2 complex2, which unexpectedly reveals two different conformations of the motor subunit tails. One tail forms a zigzag that matches the periodicity of the IFT trains, which reinforces the auto-inhibition of dynein motor activity and the binding of multiple dynein-2 complexes along the train during anterograde transport.

    • Susan K. Dutcher
    News & Views
  • AAA ATPases constitute a large family of molecular chaperones, many of which unfold substrate proteins. Two recent cryo-EM studies of the AAA ATPase Cdc48 capture this enzyme in the midst of protein unfolding and reveal a universal substrate-threading mechanism for ring-shaped ATPases.

    • Yihong Ye
    • Di Xia
    News & Views
  • The ability of CRISPR-Cas9 to accurately and efficiently target and cleave any segment of double-stranded DNA based solely on the sequence of its loaded guide RNA has revolutionized genome editing. While many structural studies have shed light on the atomic details of DNA targeting, structures of the enzyme poised to perform catalysis have remained elusive. In this issue, Zhu, Clarke, Puppala et al. provide snapshots of the enzyme in action as it performs concerted cleavage of a target DNA1.

    • David W. Taylor
    News & Views
  • The ‘tubulin code’, a set of post-translational modifications to the microtubule cytoskeleton that include removal of the C-terminal Tyr of α-tubulin, regulates the biological function of the polymer. Three studies now report structures of VASH1–SVBP and VASH2–SVBP heterodimers and provide insights into how these proteases recognize and cleave the terminal Tyr of α-tubulin.

    • Kevin C. Slep
    News & Views
  • Abasic sites are among the most frequent DNA lesions, and when they occur within single-stranded DNA, their repair can give rise to genomic instability and mutations. One mechanism for the protection of abasic sites involves covalent attachment of 5-hydroxymethylcytosine-binding, embryonic stem cell–specific (HMCES) protein to DNA. Now, two research groups have elucidated the structural basis of the action of HMCES and its bacterial equivalent, YedK, revealing a unique and intriguing chemistry of DNA–protein crosslink formation.

    • Marcin Nowotny
    News & Views
  • Viral mRNA synthesis is an essential step in the influenza virus replication cycle and is a prime target for the development of new antivirals. New structures of the influenza virus RNA polymerase now unveil previously unknown details of influenza virus transcription.

    • Aartjan J. W. te Velthuis
    News & Views