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The second Keystone Symposium on AAA+ proteins, “AAA+ Proteins: From Atomic Structures to Organisms”, was held in Tahoe City, USA in January 2020. The program highlighted recent advances from structural, biochemical and cellular approaches that have extended our understanding of these important ATP-driven molecular machines.
Cellular protein levels are finely tuned through microRNA-mediated gene regulation, triggered by RNA-induced silencing complexes (RISCs) that recognize, bind and silence mRNA targets. A recent study shows that, while mRNA target recognition is achieved with only about a third of the guide RNA sequence, formation of an efficient RISC conformation required for target silencing involves the coordination of transient structural states of the entire guide RNA–mRNA duplex.
Lauberth and Sartorelli consider and discuss recent insights into the biogenesis and function of enhancer RNAs and the key roles they play in the regulation of gene expression.
A crystal structure of SARS-CoV-2 with inhibitor carmofur reveals the mechanism of action of this compound and opens the way to develop more potent drugs.
Transport and electrophysiology measurements of the Na+/I− symporter reveal that environmental pollutant perchlorate binds to an allosteric site and inhibits I− transport not only by competition but also by changing the stoichiometry of I− transport.
Yeast studies and mathematical modeling reveal a new variable that influences transitions between prion states and persistence of the [PSI+] phenotype: the size of the amyloid seed.
The cell cycle regulatory E3 ligase APC/C cooperates with UBE2C to prime substrates with ubiquitin and UBE2S to extend the ubiquitin chains. Careful analysis reveals that binding of the UBE2S to APC/C accelerates the rate-limiting step of APC/C–UBE2C.
Structural analysis and functional assays of S. aureus LtaA reveal that it functions as a proton-coupled flippase of the lipoteichoic acid precursor and that it contributes to S. aureus survival under physiological acidic conditions.
A crystal structure of human ESCRT-I headpiece reveals a helical assembly that is required for autophagosome closure and HIV-1 release in cells. The work suggests that ESCRT-I assembly templates ESCRT-III assembly for membrane scission.
Mixed tailing of hepatitis B virus and human cytomegalovirus transcripts via recruitment of the TENT4–ZCCHC14 complex by a common RNA element protects viral RNAs from degradation.
Cryo-EM visualization of the bacterial pore-forming toxin VopQ bound to its host V-ATPase membrane-domain target reveals how cytotoxic effector proteins promote membrane disruption and inhibit ATPase function.
A cryo-EM structure of amyloid fibrils formed in vitro with recombinant human PrP provides insights into fibril architecture and the potential role of disease mutations.