Articles in 2021

The cryo-EM structure of DNA-assembled histone pairs Hβ-Hα and Hδ-Hγ from Marseillevirus, a nucleocytoplasmic large DNA virus, reveals that these proteins form viral nucleosomes with highly conserved features when compared to canonical eukaryotic nucleosomes.

Structural and functional analyses of RNA polymerase II−nucleosome complexes reveal how the chromatin remodeler Chd1 and the histone chaperone FACT mediate Pol II transcription through a nucleosome.

Cryo-EM structures of assembly intermediates of the proteasome 20S core particle show how the coordinated activity of chaperones orchestrates early steps in proteasome biogenesis.

Cryo–EM reconstructions and atomic models reveal the mechanism of MutS–MutL DNA mismatch recognition and repair initiation.

Structures of USP1−UAF complexes, including a cryo-EM structure of USP−UAF1 bound to its substrate FANCI−FANCD2, reveal molecular details of USP1−UAF1 regulation and substrate recognition.

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.

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 G_i 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.

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.

The authors describe the development of ASPIR-1, a small molecule that specifically inhibits AAA proteins by covalently modifying a cysteine residue introduced by mutagenesis at the AAA ATPase site.

Cryo-EM structures of the E. coli ABC transporter LolCDE in different functional states reveal mechanism of lipoprotein transport to the outer membrane of Gram-negative bacteria.

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.

The kinetics of prion aggregation are now dissected in mice, revealing slower PrP^Sc replication in vivo than in vitro and the contribution of aggregate fragmentation.

Inefficiently spliced first exons of enhancer-generated lncRNAs and promoter-antisense lncRNAs trigger a transcription termination checkpoint that requires WDR82, an RNA Pol II–binding protein, and its RNA-binding partner, ZC3H4.

A new cryo-EM structure of the ~1 MDa Escherichia coli cellulose synthase macrocomplex reveals how cellulose biosynthesis and phosphoethanolamine (pEtN) modification are coupled to promote host-tissue adhesion.

Cryo-EM structures of the Fanconi anemia core complex reveal insights into the remodeling of the FANCI–FANCD2 DNA clamp, which is essential during the repair of DNA interstrand crosslinks.

The antiparasitic drug suramin directly inhibits SARS-CoV-2 RNA-dependent RNA polymerase by blocking binding of the RNA template–primer duplex and entry of nucleotide triphosphate to the catalytic site.

Recent structures of eukaryotic membrane protein insertases of the Oxa1 superfamily reveal a conserved protein module and common mechanistic principles that enable membrane insertion of a diverse set of substrates.

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.

A cryo-EM structure of the striatin-interacting phosphatase and kinase (STRIPAK) complex reveals the overall architecture of this large, multisubunit assembly that broadly regulates different signaling pathways.