Reviews & Analysis

Filter by:

  • The biogenesis of eukaryotic 20S proteasomes requires the accurate assembly of 14 closely related protein subunits and occurs in a complex series of chaperone-dependent steps. Important insights into this pathway are now provided by the high-resolution cryo-EM structures of two 20S proteasome assembly intermediates.

    • Edward P. Morris
    • Paula C. A. da Fonseca
    News & Views
  • NLRP1 was the first inflammasome-forming sensor to be identified, but only recently has its mode of action been in the spotlight. Two groups now report cryo-EM structures demonstrating how NLRP1 is kept in check by the dipeptidyl peptidase DPP9, and they illuminate how DPP9 inhibition leads to NLRP1 inflammasome activation.

    • Stefan Bauernfried
    • Veit Hornung
    News & Views
  • The interaction of G protein–coupled receptors (GPCRs) with heterotrimeric G proteins plays a critical role in signal transduction processes, and multiple GPCR–G protein complexes reconstituted in detergent micelles have been visualized using cryo-EM. A new study reports the structure of neurotensin receptor 1 (NTSR1) in complex with the heterotrimeric Gi protein, assembled in a lipid environment using circularized nanodiscs. The structure sheds light on how the lipid context may influence receptor–G protein coupling and activation.

    • Jagannath Maharana
    • Arun K. Shukla
    News & Views
  • AAA+ proteins (ATPases associated with various cellular activities) catalyze the energy-dependent movement or rearrangement of macromolecules. A new study addresses the important question of how to design a selective chemical inhibitor for specific proteins in this diverse superfamily. The powerful chemical genetics approach adds to a growing toolbox of applications that allow dissection of the functions of distinct AAA+ proteins in vivo, facilitating the first steps toward effective drug development.

    • Saša Petrović
    • Petra Wendler
    News & Views
  • Pervasive genome-wide transcription initiation by RNA polymerase II (Pol II) necessitates mechanisms that restrain the quantity and length of the transcripts. A new study investigates a mechanism for inducing early transcription termination, employed primarily at genomic regions producing noncoding RNAs.

    • Noa Gil
    • Igor Ulitsky
    News & Views
  • The highly conserved striatin-interacting phosphatase and kinase (STRIPAK) multimeric complex regulates the Hippo signaling pathway through phosphatase activity. A recent structure of the core STRIPAK hub reveals how striatins tetramerize to serve as a scaffolding platform for the assembly of an intricate architecture, which is distinct from that of all other protein phosphatase 2A (PP2A) complexes.

    • Wei Huang
    • Daniel Leonard
    • Derek J. Taylor
    News & Views
  • Resolving RNA polymerase structures at the atomic level has revolutionized our understanding of transcription. Three articles now published in Nature Structural & Molecular Biology and Nature Communications decipher unique properties of human RNA polymerase III and propose built-in modules within the enzyme that mediate transcriptional activation, repression and antirepression.

    • Elisabeth Lata
    • Martin Teichmann
    News & Views
  • The multipass transmembrane protein UNC93B1 is critical for the proper trafficking and function of many members of the Toll-like receptor (TLR) family of innate immune receptors. A new study reports two structures of UNC93B1 in complex with full-length TLR3 or TLR7 and sheds light on how this single chaperone may differentially interact with and regulate the function of individual TLRs.

    • Victoria E. Rael
    • Gregory M. Barton
    News & Views
  • NUP98 is one of the most promiscuous fusion partners involved in leukemogenic chromosomal translocations, but the myriad of partners has long obfuscated the mechanism by which these fusion proteins drive leukemia. A new mass spectrometry–based approach has produced clues that suggest an entirely new model of leukemogenesis.

    • Christopher I. Slape
    News & Views
  • The multisubunit phospholipid transport system Mla has been under scrutiny to determine whether it functions as an exporter or an importer. Structural studies accompanied by the reconstitution of the entire Mla system into proteoliposomes now reveal that ATP binding and hydrolysis drive phospholipid import.

    • Russell E. Bishop
    News & Views
  • The protein SARM1 is an executioner of axon degeneration through its NAD+ hydrolase activity. Three groups now report structures of human SARM1 in an inactive state and identify NAD+ as an allosteric inhibitor, illuminating an elegant mechanism of how SARM1 is activated at lower NAD+ levels and causes NAD+ collapse and axon degeneration.

    • Liang Tong
    News & Views
  • Three recent studies report cryo-EM structures of amyloid fibrils of islet amyloid polypeptide (IAPP), which are linked to type 2 diabetes (T2D) pathogenesis. The results shed light on the structural basis of IAPP fibril formation, reveal remarkable similarities between IAPP and Aβ fibrils and will inform the design of anti-amyloid drugs in T2D and Alzheimer’s disease (AD).

    • Aphrodite Kapurniotu
    News & Views
  • BAX and BAK oligomerize to mediate mitochondrial membrane permeabilization during apoptosis. A recent structure of the core domain of active BAK dimers with bound phospholipid molecules reveals a new bridging mechanism by which lipids drive BAX and BAK oligomerization and membrane pore formation.

    • Hector Flores-Romero
    • Ana J. García-Sáez
    News & Views
  • In situ structures of the spirochete flagellar motor by cryo-ET reveal two distinct modes of interactions between the rotor ring and stator units. Together with new cryo-EM structures of the isolated stator units, this work provides insights into the mechanisms of torque generation and directional switch.

    • Keiichi Namba
    News & Views
  • During translesion synthesis, eukaryotic DNA polymerase ζ carries out extension from a wide range of DNA lesions. Elucidation of the cryo-EM structure of polymerase ζ reveals how the enzyme catalyzes DNA strand synthesis beyond the lesion.

    • M. Todd Washington
    • Melissa S. Gildenberg
    News & Views